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Do folate, vitamins B₆ and B₁₂ play a role in the pathogenesis of migraine? The role of pharmacoepigenomics

Shaik MM, Tan HL, Kamal MA, Gan SH

CNS Neurol Disord Drug Targets, 2014;13(5):828-35.
PMID: 24040787

Migraine is a neurovascular disease that has classically been attributed to multifactorial aetiologies, with genetic components and environmental interactions considered the main influence. Genes such as flavoenzyme 5, 10- methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma homocysteine levels. This elevation in homocysteine results in an array of metabolic disorders and increased risk of complex diseases, including migraine. Catalysation of homocysteine requires the presence of vitamins B6, B12 and folate. Deficiencies in these cofactor vitamins result in hypomethylation, which triggers migraine. Because migraine predominantly affects females, it is hypothesised that fluctuating oestrogen levels, which are governed by oestrogen receptor 1 polymorphisms, are important. Another important factor is homocysteine, the production of which is dependent upon MTHFR and B vitamins. Gene expression is modulated through epigenetic mechanisms, which involve methionine. Additionally, folate plays a major role in DNA synthesis. We propose that vitamin B intake, coupled with MTHFR and oestrogen receptor 1 polymorphisms, causes differential DNA methylation and gene expression that may contribute to the occurrence of migraine.
Stem cells in stroke repair: current success and future prospects

Gopurappilly R, Pal R, Mamidi MK, Dey S, Bhonde R, Das AK

CNS Neurol Disord Drug Targets, 2011 Sep 1;10(6):741-56.
PMID: 21838668

Stroke causes a devastating insult to the brain resulting in severe neurological deficits because of a massive loss of different neurons and glia. In the United States, stroke is the third leading cause of death. Stroke remains a significant clinical unmet condition, with only 3% of the ischemic patient population benefiting from current treatment modalities, such as the use of thrombolytic agents, which are often limited by a narrow therapeutic time window. However, regeneration of the brain after ischemic damage is still active days and even weeks after stroke occurs, which might provide a second window for treatment. Neurorestorative processes like neurogenesis, angiogenesis and synaptic plasticity lead to functional improvement after stroke. Stem cells derived from various tissues have the potential to perform all of the aforementioned processes, thus facilitating functional recovery. Indeed, transplantation of stem cells or their derivatives in animal models of cerebral ischemia can improve function by replacing the lost neurons and glial cells and by mediating remyelination, and modulation of inflammation as confirmed by various studies worldwide. While initially stem cells seemed to work by a 'cell replacement' mechanism, recent research suggests that cell therapy works mostly by providing trophic support to the injured tissue and brain, fostering both neurogenesis and angiogenesis. Moreover, ongoing human trials have encouraged hopes for this new method of restorative therapy after stroke. This review describes up-to-date progress in cell-based therapy for the treatment of stroke. Further, as we discuss here, significant hurdles remain to be addressed before these findings can be responsibly translated to novel therapies. In particular, we need a better understanding of the mechanisms of action of stem cells after transplantation, the therapeutic time window for cell transplantation, the optimal route of cell delivery to the ischemic brain, the most suitable cell types and sources and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment. An integrated approach of cell-based therapy with early-phase clinical trials and continued preclinical work with focus on mechanisms of action is needed.
An insight into the role of Artificial Intelligence in the early diagnosis of Alzheimer's disease

Verma RK, Pandey M, Chawla P, Choudhury H, Mayuren J, Bhattamisra SK, et al.

CNS Neurol Disord Drug Targets, 2021 May 11.
PMID: 33982657 DOI: 10.2174/1871527320666210512014505

BACKGROUND: The complication of Alzheimer's disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the foremost hurdle behind its treatment. Several studies have aimed to identify potential biomarkers that can be detected in body fluids (CSF, blood, urine, etc) or assessed by neuroimaging (i.e., PET and MRI). However, the clinical implementation of these biomarkers is incomplete as they cannot be validated.
METHOD: To overcome the limitation, the use of artificial intelligence along with technical tools has been extensively investigated for AD diagnosis. For developing a promising artificial intelligence strategy that can diagnose AD early, it is critical to supervise neuropsychological outcomes and imaging-based readouts with a proper clinical review.
CONCLUSION: Profound knowledge, a large data pool, and detailed investigations are required for the successful implementation of this tool. This review will enlighten various aspects of early diagnosis of AD using artificial intelligence.
Modeling Parkinson's Disease in Zebrafish

Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al.

CNS Neurol Disord Drug Targets, 2020;19(5):386-399.
PMID: 32640968 DOI: 10.2174/1871527319666200708124117

Parkinson's Disease (PD) is one of the most common neurodegenerative disorders that affects the motor system, and includes cardinal motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to the increase in life span. Although, two centuries since the first description of the disease, no proper cure with regard to treatment strategies and control of symptoms could be reached. One of the major challenges faced by the researchers is to have a suitable research model. Rodents are the most common PD models used, but no single model can replicate the true nature of PD. In this review, we aim to discuss another animal model, the zebrafish (Danio rerio), which is gaining popularity. Zebrafish brain has all the major structures found in the mammalian brain, with neurotransmitter systems, and it also possesses a functional blood-brain barrier similar to humans. From the perspective of PD research, the zebrafish possesses the ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. We summarize the various zebrafish models available to study PD, namely chemical-induced and genetic models. The zebrafish can complement the use of other animal models for the mechanistic study of PD and help in the screening of new potential therapeutic compounds.
Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches

Bhattamisra SK, Shin LY, Saad HIBM, Rao V, Candasamy M, Pandey M, et al.

CNS Neurol Disord Drug Targets, 2020;19(3):174-183.
PMID: 32418534 DOI: 10.2174/1871527319666200518102130

The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords "insulin"; "insulin resistance"; "Alzheimer's disease"; "Parkinson's disease" in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.
C-Abl Inhibition; A Novel Therapeutic Target for Parkinson's Disease

Abushouk AI, Negida A, Elshenawy RA, Zein H, Hammad AM, Menshawy A, et al.

CNS Neurol Disord Drug Targets, 2018 Apr 26;17(1):14-21.
PMID: 28571531 DOI: 10.2174/1871527316666170602101538

Parkinson's disease (PD) is the most prevalent movement disorder in the world. The major pathological hallmarks of PD are death of dopaminergic neurons and the formation of Lewy bodies. At the moment, there is no cure for PD; current treatments are symptomatic. Investigators are searching for neuroprotective agents and disease modifying strategies to slow the progress of neurodegeneration. However, due to lack of data about the main pathological sequence of PD, many drug targets failed to provide neuroprotective effects in human trials. Recent evidence suggests the involvement of C-Abelson (c-Abl) tyrosine kinase enzyme in the pathogenesis of PD. Through parkin inactivation, alpha synuclein aggregation, and impaired autophagy of toxic elements. Experimental studies showed that (1) c-Abl activation is involved in neurodegeneration and (2) c-Abl inhibition shows neuroprotective effects and prevents dopaminergic neuronal' death. Current evidence from experimental studies and the first in-human trial shows that c-Abl inhibition holds the promise for neuroprotection against PD and therefore, justifies the movement towards larger clinical trials. In this review article, we discussed the role of c-Abl in PD pathogenesis and the findings of preclinical experiments and the first in-human trial. In addition, based on lessons from the last decade and current preclinical evidence, we provide recommendations for future research in this area.
Metabolic Syndrome and Its Effect on the Brain: Possible Mechanism

Arshad N', Lin TS, Yahaya MF

CNS Neurol Disord Drug Targets, 2018;17(8):595-603.
PMID: 30047340 DOI: 10.2174/1871527317666180724143258

BACKGROUND & OBJECTIVE: Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer's disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease.
CONCLUSION: In this review, we will discuss the possible mechanisms which may relate the association between MetS and cognitive decline which include vascular damages, elevation of reactive oxygen species (ROS), insulin resistance and low-grade inflammation.
Light-Emitting Diode (LED) Therapy Attenuates Neurotoxicity of Methanol-Induced Memory Impairment and Apoptosis in The Hippocampus

Ghanbari A, Zibara K, Salari S, Ghareghani M, Rad P, Mohamed W, et al.

CNS Neurol Disord Drug Targets, 2018;17(7):528-538.
PMID: 29968547 DOI: 10.2174/1871527317666180703111643

BACKGROUND & OBJECTIVE: The adolescent brain has a higher vulnerability to alcoholinduced neurotoxicity, compared to adult's brain. Most studies have investigated the effect of ethanol consumption on the body, however, methanol consumption, which peaked in the last years, is still poorly explored.
METHOD: In this study, we investigated the effects of methanol neurotoxicity on memory function and pathological outcomes in the hippocampus of adolescent rats and examined the efficacy of Light- Emitting Diode (LED) therapy. Methanol induced neurotoxic rats showed a significant decrease in the latency period, in comparison to controls, which was significantly improved in LED treated rats at 7, 14 and 28 days, indicating recovery of memory function. In addition, methanol neurotoxicity in hippocampus caused a significant increase in cell death (caspase3+ cells) and cell edema at 7 and 28 days, which were significantly decreased by LED therapy. Furthermore, the number of glial fibrillary acid protein astrocytes was significantly lower in methanol rats, compared to controls, whereas LED treatment caused their significant increase. Finally, methanol neurotoxicity caused a significant decrease in the number of brain-derived neurotrophic factor (BDNF+) cells, but also circulating serum BDNF, at 7 and 28 days, compared to controls, which were significantly increased by LED therapy. Importantly, LED significantly increased the number of Ki-67+ cells and BDNF levels in the serum and hypothalamus in control-LED rats, compared to controls without LED therapy.
CONCLUSION: In conclusion, chronic methanol administration caused severe memory impairments and several pathological outcomes in the hippocampus of adolescent rats which were improved by LED therapy.
Scopolamine, a Toxin-Induced Experimental Model, Used for Research in Alzheimer's Disease

Chen WN, Yeong KY

CNS Neurol Disord Drug Targets, 2020;19(2):85-93.
PMID: 32056532 DOI: 10.2174/1871527319666200214104331

Scopolamine as a drug is often used to treat motion sickness. Derivatives of scopolamine have also found applications as antispasmodic drugs among others. In neuroscience-related research, it is often used to induce cognitive disorders in experimental models as it readily permeates the bloodbrain barrier. In the context of Alzheimer's disease, its effects include causing cholinergic dysfunction and increasing amyloid-β deposition, both of which are hallmarks of the disease. Hence, the application of scopolamine in Alzheimer's disease research is proven pivotal but seldom discussed. In this review, the relationship between scopolamine and Alzheimer's disease will be delineated through an overall effect of scopolamine administration and its specific mechanisms of action, discussing mainly its influences on cholinergic function and amyloid cascade. The validity of scopolamine as a model of cognitive impairment or neurotoxin model will also be discussed in terms of advantages and limitations with future insights.
Stingless Bee Honey Reduces Anxiety and Improves Memory of the Metabolic Disease-induced Rats

Arshad N', Lin TS, Yahaya MF

CNS Neurol Disord Drug Targets, 2020;19(2):115-126.
PMID: 31957619 DOI: 10.2174/1871527319666200117105133

BACKGROUND: Scientific studies support the evidence of the involvement of Metabolic Syndrome (MetS) in the progression of neurodegenerative diseases through oxidative stress. Consumption of antioxidant compounds was found to be beneficial for brain-health as it reduced the brain oxidative stress level and improved cognitive performance in animals. Stingless bee honey or locally known as Kelulut Honey (KH) has high phenolic content and is widely used as a food supplement.
OBJECTIVES: In this study, we aimed to investigate the effects of KH on the brain of MetS-induced rats.
METHODS: Forty male Wistar rats were divided into 5 groups; 8 weeks (C8) and 16 weeks control groups (C16), groups that received High-Carbohydrate High Fructose (HCHF) diet for 8 weeks (MS8) and 16 weeks (MS16), and a group that received HCHF for 16 weeks with KH supplemented for the last 35 days (KH).
RESULTS: Serum fasting blood glucose decreased in the KH group compared to the MS16 group. HDL levels were significantly decreased in MetS groups compared to control groups. Open field experiments showed that KH group exhibits less anxious behavior compared to the MetS group. Probe trial of Morris water maze demonstrated significant memory retention of KH group compared to the MS16 group. Nissl staining showed a significant decrease in the pyramidal hippocampal cells in the MS16 compared to the KH group.
CONCLUSION: KH has the ability to normalise blood glucose and reduce serum triglyceride and LDL levels in MetS rats, while behavior studies complement its effect on anxiety and memory. This shows a promising role of KH in attenuating neurodegenerative diseases through the antioxidant activity of its polyphenolic content.
Causes and Consequences of MicroRNA Dysregulation Following Cerebral Ischemia-Reperfusion Injury

Forouzanfar F, Shojapour M, Asgharzade S, Amini E

CNS Neurol Disord Drug Targets, 2019;18(3):212-221.
PMID: 30714533 DOI: 10.2174/1871527318666190204104629

Stroke continues to be a major cause of death and disability worldwide. In this respect, the most important mechanisms underlying stroke pathophysiology are inflammatory pathways, oxidative stress, as well as apoptosis. Accordingly, miRNAs are considered as non-coding endogenous RNA molecules interacting with their target mRNAs to inhibit mRNA translation or reduce its transcription. Studies in this domain have similarly shown that miRNAs are strongly associated with coronary artery disease and correspondingly contributed to the brain ischemia molecular processes. To retrieve articles related to the study subject, i.e. the role of miRNAs involved in inflammatory pathways, oxidative stress, and apoptosis in stroke from the databases of Web of Science, PubMed (NLM), Open Access Journals, LISTA (EBSCO), and Google Scholar; keywords including cerebral ischemia, microRNA (miRNA), inflammatory pathway, oxidative stress, along with apoptosis were used. It was consequently inferred that, miRNAs could be employed as potential biomarkers for diagnosis and prognosis, as well as therapeutic goals of cerebral ischemia.
The Mechanism of Action of Salsolinol in Brain: Implications in Parkinson's Disease

Voon SM, Ng KY, Chye SM, Ling APK, Voon KGL, Yap YJ, et al.

CNS Neurol Disord Drug Targets, 2020;19(10):725-740.
PMID: 32881676 DOI: 10.2174/1871527319666200902134129

1-Methyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol, commonly known as salsolinol, is a compound derived from dopamine. It was first discovered in 1973 and has gained attention for its role in Parkinson's disease. Salsolinol and its derivatives were claimed to play a role in the pathogenesis of Parkinson's disease as a neurotoxin that induces apoptosis of dopaminergic neurons due to its structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its ability to induce Parkinsonism. In this article, we discussed the biosynthesis, distribution and blood-brain barrier permeability of salsolinol. The roles of salsolinol in a healthy brain, particularly the interactions with enzymes, hormone and catecholamine, were reviewed. Finally, we discussed the involvement of salsolinol and its derivatives in the pathogenesis of Parkinson's disease.
Beyond the Obvious: Smoking and Respiratory Infection Implications on Alzheimer's Disease

Wadhwa R, Paudel KR, Mehta M, Shukla SD, Sunkara K, Prasher P, et al.

CNS Neurol Disord Drug Targets, 2020;19(9):698-708.
PMID: 33109069 DOI: 10.2174/1871527319999200817112427

Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders, and lung and oral cancers, but also causes neurological disorders such as Alzheimer 's disease. Tobacco smoke consists of more than 4500 toxic chemicals, which form free radicals and can cross blood-brain barrier resulting in oxidative stress, an extracellular amyloid plaque from the aggregation of amyloid β (Aβ) peptide deposition in the brain. Further, respiratory infections such as Chlamydia pneumoniae, respiratory syncytial virus have also been involved in the induction and development of the disease. The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. The review article sheds light on the role of smoking and respiratory infections in causing oxidative stress and neuroinflammation, resulting in Alzheimer's disease (AD). This review will be of interest to scientists and researchers from biological and medical science disciplines, including microbiology, pharmaceutical sciences and the translational researchers, etc. The increasing understanding of the relationship between chronic lung disease and neurological disease is two-fold. First, this would help to identify the risk factors and possible therapeutic interventions to reduce the development and progression of both diseases. Second, this would help to reduce the probable risk of development of AD in the population prone to chronic lung diseases.
Nanoparticles Based Intranasal Delivery of Drug to Treat Alzheimer's Disease: A Recent Update

Pandey M, Choudhury H, Verma RK, Chawla V, Bhattamisra SK, Gorain B, et al.

CNS Neurol Disord Drug Targets, 2020;19(9):648-662.
PMID: 32819251 DOI: 10.2174/1871527319999200819095620

Alzheimer Association Report (2019) stated that the 6th primary cause of death in the USA is Alzheimer's Disease (AD), which leads to behaviour and cognitive impairment. Nearly 5.8 million peoples of all ages in the USA have suffered from this disease, including 5.6 million elderly populations. The statistics of the progression of this disease is similar to the global scenario. Still, the treatment of AD is limited to a few conventional oral drugs, which often fail to deliver an adequate amount of the drug in the brain. The reduction in the therapeutic efficacy of an anti-AD drug is due to poor solubility, existence to the blood-brain barrier and low permeability. In this context, nasal drug delivery emerges as a promising route for the delivery of large and small molecular drugs for the treatment of AD. This promising pathway delivers the drug directly into the brain via an olfactory route, which leads to the low systemic side effect, enhanced bioavailability, and higher therapeutic efficacy. However, few setbacks, such as mucociliary clearance and poor drug mucosal permeation, limit its translation from the laboratory to the clinic. The above stated limitation could be overcome by the adaption of nanoparticle as a drug delivery carrier, which may lead to prolong delivery of drugs with better permeability and high efficacy. This review highlights the latest work on the development of promising Nanoparticles (NPs) via the intranasal route for the treatment of AD. Additionally, the current update in this article will draw the attention of the researcher working on these fields and facing challenges in practical applicability.
Immunotherapies for Parkinson's Disease: Progression of Clinical Development

Teng JS, Ooi YY, Chye SM, Ling APK, Koh RY

CNS Neurol Disord Drug Targets, 2021;20(9):802-813.
PMID: 34042040 DOI: 10.2174/1871527320666210526160926

Parkinson's disease is a common neurodegenerative disease affecting the movement and well-being of most elderly. The manifestations of Parkinson's disease often include resting tremor, stiffness, bradykinesia, and muscular rigidity. The typical hallmark of Parkinson's disease is the destruction of neurons in the substantia nigra and the presence of Lewy bodies in different compartments of the central nervous system. Due to various limitations to the currently available treatments, immunotherapies have emerged to be the new approach to Parkinson's disease treatment. This approach shows some positive outcomes on the efficacy by removing the aggregated species of alpha-synuclein, which is believed to be one of the causes of Parkinson's disease. In this review, an overview of how alpha-synuclein contributes to Parkinson's disease and the effects of a few new immunotherapeutic treatments, including BIIB054 (cinpanemab), MEDI1341, AFFITOPE, and PRX002 (prasinezumab) that are currently under clinical development, will be discussed.
Epigenomic approach in understanding Alzheimer's disease and type 2 diabetes mellitus

Shaik MM, Gan SH, Kamal MA

CNS Neurol Disord Drug Targets, 2014 Mar;13(2):283-9.
PMID: 24074446 DOI: 10.2174/18715273113126660181

Cognitive decline is a debilitating feature of Alzheimer's disease (AD). The causes leading to such impairment are still poorly understood and effective treatments for AD are still unavailable. Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for AD due to desensitisation of insulin receptors in the brain. Recent studies have suggested that epigenetic mechanisms may also play a pivotal role in the pathogenesis of both AD and T2DM. This article describes the correlation between AD and T2DM and provides the insights to the epigenetics of AD. Currently, more research is needed to clarify the exact role of epigenetic regulation in the course and development of AD and also in relation to insulin. Research conducted especially in the earlier stages of the disease could provide more insight into its underlying pathophysiology to help in early diagnosis and the development of more effective treatment strategies.
'Non-criteria' neurologic manifestations of antiphospholipid syndrome: a hidden kingdom to be discovered

Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH

CNS Neurol Disord Drug Targets, 2016;15(10):1253-1265.
PMID: 27658514 DOI: 10.2174/1871527315666160920122750

Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.
Nanotechnological Advances in the Treatment of Epilepsy

Ali OAMA, Shaikh MF, Hasnain MS, Sami F, Khan A, Ansari MT

CNS Neurol Disord Drug Targets, 2021 Dec 21.
PMID: 34939554 DOI: 10.2174/1871527321666211221162104

Epilepsy is known as one of the major challenges for medical science. The sudden appearance of a seizure has been a significant health emergency as it may lead to further complications. Although key advancement have been achieved in terms of pharmacological approaches for epilepsy, many issues remain uncertain. Lipid carriers have been at the forefront, especially in neurodegenerative diseases such as epilepsy, Alzheimer's, dementia, etc. The blood-brain barrier still appears to be a major impediment in the successful treatment of epileptic seizures. This is mainly due to the limited bioavailability of most anti-convulsant drugs. The present review encompasses the issues underlying the current approach for epilepsy drug treatment and highlights the newer, novel, and more precise drug delivery system to manage seizures. The advantage of using a lipid-based delivery system is its superior absorption in the brain cells. Ample evidence shows that reducing the particle size also infuses the drug easily through the blood-brain barrier. The application of liposomes, polymeric nanoparticles, metallic nanoparticles, and solid lipid nanoparticles for the treatment and management of epilepsy has been highlighted in the present review. This review will provide an overview of the current status of the treatment and recent advances in the treatment of epilepsy.
Functional Neuroproteomics: An Imperative Approach for Unravelling Protein Implicated Complexities of Brain

Husain I, Ahmad W, Ali A, Anwar L, Nuruddin SM, Ashraf K, et al.

CNS Neurol Disord Drug Targets, 2021;20(7):613-624.
PMID: 33530918 DOI: 10.2174/1871527320666210202121624

A proteome is defined as a comprehensive protein set either of an organ or an organism at a given time and under specific physiological conditions. Accordingly, the study of the nervous system's proteomes is called neuroproteomics. In the neuroproteomics process, various pieces of the nervous system are "fragmented" to understand the dynamics of each given sub-proteome in a much better way. Functional proteomics addresses the organisation of proteins into complexes and the formation of organelles from these multiprotein complexes that control various physiological processes. Current functional studies of neuroproteomics mainly talk about the synapse structure and its organisation, the major building site of the neuronal communication channel. The proteomes of synaptic vesicle, presynaptic terminal, and postsynaptic density, have been examined by various proteomics techniques. The objectives of functional neuroproteomics are: to solve the proteome of single neurons or astrocytes grown in cell cultures or from the primary brain cells isolated from tissues under various conditions, to identify the set of proteins that characterize specific pathogenesis, or to determine the group of proteins making up postsynaptic or presynaptic densities. It is usual to solve a particular sub-proteome like the heat-shock response proteome or the proteome responding to inflammation. Post-translational protein modifications alter their functions and interactions. The techniques to detect synapse phosphoproteome are available. However, techniques for the analysis of ubiquitination and sumoylation are under development.
MicroRNA Dysregulation in Alzheimer's Disease

Putteeraj M, Fairuz YM, Teoh SL

CNS Neurol Disord Drug Targets, 2017;16(9):1000-1009.
PMID: 28782488 DOI: 10.2174/1871527316666170807142311

BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD) is arguably the largest healthcare issue of our time. AD is thought to be principally the result of an inter-play between the β-amyloid peptide and Tau, and it is driven by several genetic and environmental risk factors. Recent studies have shown that small non-protein-coding microRNA (miRNA) and the associated post-transcriptional gene regulation are important regulators of many neurodegenerative diseases, including AD. We reviewed recent studies identifying various miRNA dysregulated in AD. These miRNAs could play a significant role in the pathophysiology of AD, in both β-amyloid peptide and Tau toxicity.
CONCLUSION: The identification of dysregulated miRNAs pattern can serve as specific AD biomarkers which may provide the basis for new and effective diagnostic approach. In addition, these miRNAs may represent new targets for pharmaceutical development.

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