INPP5D/SHIP1: Expression, Regulation and Roles in Alzheimer's Disease Pathophysiology.

Alzheimer's disease (AD) is the most common form of dementia, accounting for approximately 38.5 million cases of all-cause dementia. Over 60% of these individuals live in low- and middle-income countries and are the worst affected, especially by its deleterious effects on the productivity of both patients and caregivers. Numerous risk factors for the disease have been identified and our understanding of gene-environment interactions have shed light on several gene variants that contribute to the most common, sporadic form of AD. Microglial cells, the innate immune cells of the central nervous system (CNS), have long been established as guardians of the brain by providing neuroprotection and maintaining cellular homeostasis. A protein with a myriad of effects on various important signaling pathways that is expressed in microglia is the Src Homology 2 (SH2) domain-containing Inositol 5' Phosphatase 1 (SHIP1) protein. Encoded by the INPP5D (Inositol Polyphosphate-5-Phosphatase D) gene, SHIP1 has diminutive effects on most microglia signaling processes. Polymorphisms of the INPP5D gene have been found to be associated with a significantly increased risk of AD. Several studies have elucidated mechanistic processes by which SHIP1 exerts its perturbations on signaling processes in peripheral immune cells. However, current knowledge of the controllers of INPP5D/SHIP1 expression and the idiosyncrasies of its influences on signaling processes in microglia and their relevance to AD pathophysiology is limited. In this review, we summarize these discoveries and discuss the potential of leveraging INPP5D/SHIP1 as a therapeutic target for Alzheimer's disease.

Roles of Non-Coding RNA in Alzheimer's Disease Pathophysiology.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is accompanied by deficits in memory and cognitive functions. The disease is pathologically characterised by the accumulation and aggregation of an extracellular peptide referred to as amyloid-ß (Aß) in the form of amyloid plaques and the intracellular aggregation of a hyperphosphorelated protein tau in the form of neurofibrillary tangles (NFTs) that cause neuroinflammation, synaptic dysfunction, and oxidative stress. The search for pathomechanisms leading to disease onset and progression has identified many key players that include genetic, epigenetic, behavioural, and environmental factors, which lend support to the fact that this is a multi-faceted disease where failure in various systems contributes to disease onset and progression. Although the vast majority of individuals present with the sporadic (non-genetic) form of the disease, dysfunctions in numerous protein-coding and non-coding genes have been implicated in mechanisms contributing to the disease. Recent studies have provided strong evidence for the association of non-coding RNAs (ncRNAs) with AD. In this review, we highlight the current findings on changes observed in circular RNA (circRNA), microRNA (miRNA), short interfering RNA (siRNA), piwi-interacting RNA (piRNA), and long non-coding RNA (lncRNA) in AD. Variations in these ncRNAs could potentially serve as biomarkers or therapeutic targets for the diagnosis and treatment of Alzheimer's disease. We also discuss the results of studies that have targeted these ncRNAs in cellular and animal models of AD with a view for translating these findings into therapies for Alzheimer's disease.

Oxidative Stress and Antioxidants in Neurodegenerative Disorders.

Neurodegenerative disorders constitute a substantial proportion of neurological diseases with significant public health importance. The pathophysiology of neurodegenerative diseases is characterized by a complex interplay of various general and disease-specific factors that lead to the end point of neuronal degeneration and loss, and the eventual clinical manifestations. Oxidative stress is the result of an imbalance between pro-oxidant species and antioxidant systems, characterized by an elevation in the levels of reactive oxygen and reactive nitrogen species, and a reduction in the levels of endogenous antioxidants. Recent studies have increasingly highlighted oxidative stress and associated mitochondrial dysfunction to be important players in the pathophysiologic processes involved in neurodegenerative conditions. In this article, we review the current knowledge of the general effects of oxidative stress on the central nervous system, the different specific routes by which oxidative stress influences the pathophysiologic processes involved in Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis and Huntington's disease, and how oxidative stress may be therapeutically reversed/mitigated in order to stall the pathological progression of these neurodegenerative disorders to bring about clinical benefits.

Variant TREM2 Signaling in Alzheimer's Disease.

Alzheimer's disease is the most common form of dementia, accounting for as much as three-quarters of cases globally with individuals in low- and middle-income countries being worst affected. Numerous risk factors for the disease have been identified and our understanding of gene-environment interactions have shed light on several gene variants that contribute to the most common, sporadic form of Alzheimer's disease. Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is an important receptor that is crucial to the functioning of microglial cells, and variants of this protein have been found to be associated with a significantly increased risk of Alzheimer's disease. Several studies have elucidated the signaling processes involved in the normal functioning of the TREM2 receptor. However, current knowledge of the idiosyncrasies of the signaling processes triggered by stimulation of the variants of this receptor is limited. In this review, we examine the existing literature and highlight the effects that various receptor variants have on downstream signaling processes and discuss how these perturbations may affect physiologic processes in Alzheimer's disease. Despite the fact that this is a territory yet to be fully explored, the studies that currently exist report mostly quantitative effects on signaling. More mechanistic studies with the aim of providing qualitative results in terms of downstream signaling among these receptor variants are warranted. Such studies will provide better opportunities of identifying therapeutic targets that may be exploited in designing new drugs for the management of Alzheimer's disease.

Common mental health problems and associated factors among medical students of University of Ibadan, Nigeria.

BACKGROUND: The burden of mental health problems among medical students is on the increase especially when compared with their counterparts in other disciplines. This has counterproductive impact on the society. Understanding the prevalence and predictors of common mental health problems can inform early intervention to curb this menace. AIMS: This study was conducted to determine the prevalence, pattern and correlates of common mental health problems (anxiety and depression) amongst medical students of the University of Ibadan, Nigeria. METHODOLOGY: A descriptive cross-sectional survey was conducted among 690 pre-clinical and clinical medical students of the University of Ibadan. Data were analyzed using descriptive statistics, Chi-square test and binary logistic regression at p < 0.05. RESULTS: The prevalence of anxiety and depression were 26.5% and 10.1%, respectively, with 6.8% having both. Perceived risk factors included overwhelming academic workload (65.2%) and failure to meet up with academic expectations (64.1%). The predictors of comorbid anxiety and depression were: polygamous family setting (OR 2.7: 95% CI: 1.156-6.536) and preclinical studentship (OR: 6.2; 95% CI: 2.282-16.868). CONCLUSION: This study shows that the prevalence of mental health problems is high among medical students.