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MicroRNA expression changes in Parkinson's disease (PD) patients' leukocytes prior to and following deep brain stimulation (DBS)

Lilach S, Hagai B, Zvi I, Hermona S, Wael M

Am J Neurodegener Dis, 2021;10(3):28-33.
PMID: 34327050

The second most prevalent neurodegenerative disorder worldwide in the elderly is Parkinson's disease (PD). It is a major risk factor for aging. Objectives: Currently the involvement of miRNAs in the disease is mainly unclear. Additionally, the disease aetiology is complex and there are no available disease-modifying medications. Therefore, more evidence is required concerning its pathogenesis and developing new treatment modalities. Methods: Here, we studied the expression profiles of about 900 miRNAs in PD patients prior to and following deep brain stimulation (DBS) both on and following 1 hour off electrical stimulation and as compared with age and gender matched healthy control (HC) donor samples, using Affymetrix miRNA microarrays. We analysed statistically the data using Affymetrix expression console software. Results: We detected significantly altered miRNAs pre and post DBS treatment. Conclusions: Our findings indicate the involvement of miRNAs in PD. Future studies can enlarge the number of samples and use RNA sequencing platform to quantify further miRNAs in PD samples. We may also use the expression levels of miRNAs as biomarkers for PD in the blood.
Parkinson's genetics research on underrepresented AfrAbia populations: current state and future prospects

Mohamed W

Am J Neurodegener Dis, 2023;12(2):23-41.
PMID: 37213711

Parkinson's disease (PD), the most common motoric neurodegenerative illness, has been extensively researched to better understand its complex pathophysiology. Nearly 80% of genome-wide association studies have been conducted on persons of European ancestry, indicating a lack of diversity in human genetics. Disparate representation may result in disparities that impede the equitable adoption of personalized medicine and may also limit our knowledge of illness etiology. Even though Parkinson's disease (PD) is a global affliction, the AfrAbia population remains understudied. We conducted a dynamic and longitudinal bibliometric analysis to investigate existing studies on Parkinson's disease genetics in the AfrAbia area and identify data gaps and possible new research avenues. All PD papers concentrating on PD genetics were found using the search terms "Parkinson's Disease", "Genetics", and "Africa" in the PubMed/MEDLINE database. Only English publications published between 1992 and 2023 were chosen using filters. Original English-language research publications disclosing genetic results on Parkinson's disease in non-European Africans were examined for inclusion. Two sets of independent reviewers discovered and extracted pertinent data. The bibliometric study was carried out using the R software packages Bibliometrix and Biblioshiny. The narrowed search yielded 43 publications, all published between 2006 and 2022. Yet, after applying filters and considering the inclusion requirements, the search results comprise just 16 original articles out of 43 articles. There were 27 articles eliminated. This study puts emphasis on the critical need for more diverse participant demographics in Parkinson's disease investigations. AfrAbia-PD-Genetic Consortium (AAPDGC) is GP2 initiative that helps to represent AfrAbia PD genetics.
Leveraging genetic diversity to understand monogenic Parkinson's disease's landscape in AfrAbia

Mohamed W

Am J Neurodegener Dis, 2023;12(4):108-122.
PMID: 37736165

Parkinson's disease may be caused by a single highly deleterious and penetrant pathogenic variant in 5-10% of cases (monogenic). Research into these mutational disorders yields important pathophysiological insights. This article examines the phenotype, genotype, pathophysiology, and geographic and ethnic distribution of genetic forms of disease. Well established Parkinson's disease (PD) causal variants can follow an autosomal dominant (SNCA, LRRK2, and VPS35) and autosomal recessive pattern of inheritance (PRKN, PINK1, and DJ). Parkinson's disease is a worldwide condition, yet the AfrAbia population is understudied in this regard. No prevalence or incidence investigations have been conducted yet. Few studies on genetic risk factors for PD in AfrAbia communities have been reported which supported the notion that the prevalence and incidence rates of PD in AfrAbia are generally lower than those reported for European and North American populations. There have been only a handful of documented genetic studies of PD in AfrAbia and very limited cohort and case-control research studies on PD have been documented. In this article, we provide a summary of prior conducted research on monogenic PD in Africa and highlight data gaps and promising new research directions. We emphasize that monogenic Parkinson's disease is influenced by distinctions in ethnicity and geography, thereby reinforcing the need for global initiatives to aggregate large numbers of patients and identify novel candidate genes. The current article increases our knowledge of the genetics of Parkinson's disease (PD) and helps to further our knowledge on the genetic factors that contribute to PD, such as the lower penetrance and varying clinical expressivity of known genetic variants, particularly in AfrAbian PD patients.
Single-cell RNA sequencing analysis and Alzheimer's disease: a bibliometric analysis

Soreq L, Mohamed W

Am J Neurodegener Dis, 2023;12(5):133-146.
PMID: 38024391

Alzheimer's disease (AD) is a devastative disease, the 1st most frequent neurodegenerative disease worldwide. Its prevalence is increasing and early detection methods as well as potential genomic based therapeutics are urgently needed.
OBJECTIVES: To better characterize recent seq studies of AD and site recent relevant literature. Using single-cell RNA sequencing, the characteristics of neuronal cell populations in Alzheimer's disease (AD) have not been completely elucidated.
METHODS: We conducted a dynamic and longitudinal bibliometric analysis to investigate existing studies on Single-cell RNA sequencing analysis and Alzheimer's Disease and identify data gaps and possible new research avenues.
RESULTS: All AD papers concentrating on Single-cell RNA sequencing analysis were found using the search terms "Alzheimer's Disease", and "Single-cell RNA sequencing analysis" in the PubMed/MEDLINE database. Only English publications published between 2015 and 2023 were chosen using filters.
CONCLUSIONS: Original English-language research publications disclosing Single-cell RNA sequencing analysis and Alzheimer's Disease were examined for inclusion. Two sets of independent reviewers discovered and extracted pertinent data. The bibliometric study was carried out using the R software packages Bibliometrix and Biblioshiny. The narrowed search yielded 158 publications, all published between 2015 and 2023. Yet, after applying filters and considering the inclusion requirements, the search results comprise just 51 original articles out of 158 articles. There were 107 articles eliminated. The importance of the discovery of Single-cell RNA sequencing analysis and Alzheimer's Disease a decade ago only grows with time. Our results have important implications for future studies of AD and may help researchers across the world better understand the global context of the Single-cell RNA sequencing analysis and Alzheimer's Disease link. This study puts emphasis on the critical need for more diverse participant demographics in Alzheimer's disease investigations.
Medroxyprogesterone acetate attenuates demyelination, modulating microglia activation, in a cuprizone neurotoxic demyelinating mouse model

Mohammadi M, Abdi M, Alidadi M, Mohamed W, Zibara K, Ragerdi Kashani I

Am J Neurodegener Dis, 2021;10(5):57-68.
PMID: 34824899

Clinical data reported a reduction of Multiple sclerosis (MS) symptoms during pregnancy when progesterone levels are high. Medroxyprogesterone acetate (MPA) is a synthetic progestin contraceptive with unknown neuroprotective effects. This study investigated the effect of a contraceptive dose of MPA on microglia polarization and neuroinflammation in the neurotoxic cuprizone (CPZ)-induced demyelinating mouse model of MS. Mice received 1 mg of MPA weekly, achieving similar serum concentrations in human contraceptive users. Results revealed that MPA therapy significantly reduced the demyelination in the corpus callosum. In addition, MPA treatment induced a significant reduction in microglia M1-markers (iNOS, IL-1β and TNF-α) while M2-markers (Arg-1, IL-10 and TGF-β) were significantly increased. Moreover, MPA resulted in a significant decrease in the number of iNOS positive cells (M1), whereas TREM-2 positive cells (M2) significantly increased. Furthermore, MPA decreased the protein expression levels of NF-κB and NLRP3 inflammasome as well as mRNA expression levels of the downstream product IL-18. In summary, MPA reduces the level of demyelination and has an anti-inflammatory role in CNS demyelination by inducing M2 microglia polarization and suppressing the M1 phenotype through the inhibition of NF-κB and NLRP3 inflammasome. Our results suggest that MPA should be a suitable contraceptive pharmacological agent in demyelinating diseases.