Epsteinhouston8334

Medical and scientific communities have been striving to disentangle the complexity of neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD), in order to develop a cure or effective treatment for these diseases. Along this journey, it has become important to identify the early events occurring in the prodromal phases of these diseases and the disorders that increase the risk of neurodegeneration highlighting common pathological features. This strategy has led to a wealth of evidence identifying diabetes, mainly type 2 diabetes mellitus (T2DM) as a main risk factor for the onset and progression of AD and PD. Impaired glucose metabolism, insulin resistance, and mitochondrial dysfunction are features common to both type 2 diabetes mellitus (T2DM), and AD and PD, and they appear before clinical diagnosis of the two neurodegenerative diseases. CBL0137 order These could represent the strategic nodes of therapeutic intervention. Following this line of thought, a conceivable approach is to repurpose antidiabetic drugs as valuable agents that may prevent or reduce the risk of cognitive decline and neurodegeneration. This review summarizes the past and current findings that link AD and PD with T2DM, emphasizing the common pathological mechanisms. The efficacy of antidiabetic drugs, namely intranasal insulin, metformin, and thiazolidinediones, in the prevention and/or treatment of AD and PD is also discussed.This review describes neuroprotective effects mediated by pre- and post-conditioning-induced processes that act via the quantitative features of the hormetic dose response. These lead to the development of acquired resilience that can protect neuronal systems from endogenous and exogenous stresses and insult. Particular attention is directed to issues of dose optimization, inter-individual variation, and potential ways to further study and employ hormetic-based preconditioning approaches in medical and public health efforts to treat and prevent neurodegenerative disease.Some metabolic disorders, such as type 2 diabetes mellitus (T2DM) are risk factors for the development of cognitive deficits and Alzheimer's disease (AD). Epidemiological studies suggest that in people with T2DM, the risk of developing dementia is 2.5 times higher than that in the non-diabetic population. The signaling pathways that underlie the increased risk and facilitate cognitive deficits are not fully understood. In fact, the cause of memory deficits in AD is not fully elucidated. The dentate gyrus of the hippocampus plays an important role in memory formation. Hippocampal neurogenesis is the generation of new neurons and glia in the adult brain throughout life. New neurons incorporate in the granular cell layer of the dentate gyrus and play a role in learning and memory and hippocampal plasticity. A large body of studies suggests that hippocampal neurogenesis is impaired in mouse models of AD and T2DM. Recent evidence shows that hippocampal neurogenesis is also impaired in human patients exhibiting mild cognitive impairment or AD. This review discusses the role of hippocampal neurogenesis in the development of cognitive deficits and AD, and considers inflammatory and endothelial signaling pathways in T2DM that may compromise hippocampal neurogenesis and cognitive function, leading to AD.Aging is the major predictor for developing multiple neurodegenerative diseases, including Alzheimer's disease (AD) other dementias, and Parkinson's disease (PD). Senescent cells, which can drive aging phenotypes, accumulate at etiological sites of many age-related chronic diseases. These cells are resistant to apoptosis and can cause local and systemic dysfunction. Decreasing senescent cell abundance using senolytic drugs, agents that selectively target these cells, alleviates neurodegenerative diseases in preclinical models. In this review, we consider roles of senescent cells in neurodegenerative diseases and potential implications of senolytic agents as an innovative treatment.Neurodegenerative diseases are highly debilitating illnesses and a growing cause of morbidity and mortality worldwide. Mitochondrial dysfunction and impairment of mitochondrial-specific autophagy, namely mitophagy, have emerged as important components of the cellular processes underlying neurodegeneration. Defective mitophagy has been highlighted as the cause of the accumulation of damaged mitochondria, which consequently leads to cellular dysfunction and/or death in neurodegenerative diseases. Here, we highlight the recent advances in the molecular mechanisms of mitochondrial homeostasis and mitophagy in neurodegenerative diseases. In particular, we evaluate how mitophagy is altered in Alzheimer's, Parkinson's, and Huntington's diseases, as well as in amyotrophic lateral sclerosis, and the potential of restoring mitophagy as a therapeutic intervention. We also discuss the interlinked connections between mitophagy and innate immunity (e.g., the involvement of Parkin, interferons and TRIM21) as well as the opportunity these pathways provide to develop combinational therapeutic strategies targeting them and related molecular mechanisms in such neurodegenerative diseases.Alzheimer's disease (AD) and Parkinson's disease (PD) are, respectively, the most prevalent and fastest growing neurodegenerative diseases worldwide. The former is primarily characterized by memory loss and the latter by the motor symptoms of tremor and bradykinesia. Both AD and PD are progressive diseases that share several key underlying mitochondrial, inflammatory, and other metabolic pathologies. This review will detail how these pathologies intersect with ketone body metabolism and signaling, and how ketone bodies, particularly d-β-hydroxybutyrate (βHB), may serve as a potential adjunctive nutritional therapy for two of the world's most devastating conditions.With the lack of success and increasing urgency for therapies capable of impacting Alzheimer's disease (AD) and its progression, there are increasing efforts to expand testing of new mechanistic hypotheses to attack the disease from different angles. Three such hypotheses are the "Mitochondrial Cascade (MC)" hypothesis, the "Endo-Lysosomal Dysfunction (ELD)" hypothesis and the "Type 3 Diabetes (T3D)" hypothesis. These hypotheses provide a rationale for new pharmacological approaches to address the mitochondrial, endo-lysosomal and metabolic dysfunction associated with AD. It is increasingly evident that there is critical interplay between the metabolic dysfunction associated with obesity/metabolic syndrome/type 2 diabetes mellitus (T2DM) and patient susceptibility to AD development. A candidate for a common mechanism linking these metabolically-driven disease states is chronically-activated mechanistic target of rapamycin (mTOR) signaling. Unrestrained chronic mTOR activation may be responsible for sustaining metabolic, lysosomal and mitochondrial dysfunction in AD, driving both the breakdown of the blood-brain barrier via endothelial cell dysfunction and hyperphosphorylation of tau and formation of amyloid plaques in the brain.