Occurrence Of Neurodegenerative Disorders Research Articles

Chaperone-mediated autophagy: Molecular mechanisms, biological functions, and diseases.

Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway that eliminates substrate proteins through heat-shock cognate protein 70 recognition and lysosome-associated membrane protein type 2A-assisted translocation. It is distinct from macroautophagy and microautophagy. In recent years, the regulatory mechanisms of CMA have been gradually enriched, including the newly discovered NRF2 and p38-TFEB signaling, as positive and negative regulatory pathways of CMA, respectively. Normal CMA activity is involved in the regulation of metabolism, aging, immunity, cell cycle, and other physiological processes, while CMA dysfunction may be involved in the occurrence of neurodegenerative disorders, tumors, intestinal disorders, atherosclerosis, and so on, which provides potential targets for the treatment and prediction of related diseases. This article describes the general process of CMA and its role in physiological activities and summarizes the connection between CMA and macroautophagy. In addition, human diseases that concern the dysfunction or protective role of CMA are discussed. Our review deepens the understanding of the mechanisms and physiological functions of CMA and provides a summary of past CMA research and a vision of future directions.

Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents.

Nuclear factor kappa B (NF-κB) signaling pathways progress inflammation and immune cell differentiation in the host immune response; however, the uncontrollable stimulation of NF-κB signaling is responsible for several inflammatory illnesses regardless of whether the conditions are acute or chronic. Innate immune cells, such as macrophages, microglia, and Kupffer cells, secrete pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, via the activation of NF-κB subunits, which may lead to the damage of normal cells, including neurons, cardiomyocytes, hepatocytes, and alveolar cells. This results in the occurrence of neurodegenerative disorders, cardiac infarction, or liver injury, which may eventually lead to systemic inflammation or cancer. Recently, ginsenosides from Panax ginseng, a historical herbal plant used in East Asia, have been used as possible options for curing inflammatory diseases. All of the ginsenosides tested target different steps of the NF-κB signaling pathway, ameliorating the symptoms of severe illnesses. Moreover, ginsenosides inhibit the NF-κB-mediated activation of cancer metastasis and immune resistance, significantly attenuating the expression of MMPs, Snail, Slug, TWIST1, and PD-L1. This review introduces current studies on the therapeutic efficacy of ginsenosides in alleviating NF-κB responses and emphasizes the critical role of ginsenosides in severe inflammatory diseases as well as cancers.

Pharmacological Treatment of Alzheimer's Disease: Insights from Drosophila melanogaster.

Aging is an ineluctable law of life. During the process of aging, the occurrence of neurodegenerative disorders is prevalent in the elderly population and the predominant type of dementia is Alzheimer’s disease (AD). The clinical symptoms of AD include progressive memory loss and impairment of cognitive functions that interfere with daily life activities. The predominant neuropathological features in AD are extracellular β-amyloid (Aβ) plaque deposition and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Because of its complex pathobiology, some tangible treatment can only ameliorate the symptoms, but not prevent the disease altogether. Numerous drugs during pre-clinical or clinical studies have shown no positive effect on the disease outcome. Therefore, understanding the basic pathophysiological mechanism of AD is imperative for the rational design of drugs that can be used to prevent this disease. Drosophila melanogaster has emerged as a highly efficient model system to explore the pathogenesis and treatment of AD. In this review we have summarized recent advancements in the pharmacological research on AD using Drosophila as a model species, discussed feasible treatment strategies and provided further reference for the mechanistic study and treatment of age-related AD.

Uncoupling protein 2 haplotype does not affect human brain structure and function in a sample of community-dwelling older adults.

Uncoupling protein 2 (UCP2) is a mitochondrial membrane protein that plays a role in uncoupling electron transport from adenosine triphosphate (ATP) formation. Polymorphisms of the UCP2 gene in humans affect protein expression and function and have been linked to survival into old age. Since UCP2 is expressed in several brain regions, we investigated in this study whether UCP2 polymorphisms might 1) affect occurrence of neurodegenerative or mental health disorders and 2) affect measures of brain structure and function. We used structural magnetic resonance imaging (MRI), diffusion-weighted MRI and resting-state functional MRI in the neuroimaging sub-study of the Whitehall II cohort. Data from 536 individuals aged 60 to 83 years were analyzed. No association of UCP2 polymorphisms with the occurrence of neurodegenerative disorders or grey and white matter structure or resting-state functional connectivity was observed. However, there was a significant effect on occurrence of mood disorders in men with the minor alleles of -866G>A (rs659366) and Ala55Val (rs660339)) being associated with increasing odds of lifetime occurrence of mood disorders in a dose dependent manner. This result was not accompanied by effects of UCP2 polymorphisms on brain structure and function, which might either indicate that the sample investigated here was too small and underpowered to find any significant effects, or that potential effects of UCP2 polymorphisms on the brain are too subtle to be picked up by any of the neuroimaging measures used.

Neuroprotective molecular mechanisms of (−)-epigallocatechin-3-gallate: a reflective outcome of its antioxidant, iron chelating and neuritogenic properties

Tea, the major source of dietary flavonoids, particularly the epicatechins, signifies the second most frequently consumed beverage worldwide, which varies its status from a simple ancient cultural drink to a nutrient component, endowed possible beneficial neuro-pharmacological actions. Accumulating evidence suggests that oxidative stress, resulting in reactive oxygen species generation, plays a pivotal role in neurodegenerative diseases, supporting the implementation of radical scavengers and metal chelating agents, such as natural tea polyphenols, for therapy. Vast epidemiology data indicate a correlation between occurrence of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, and green tea consumption. In particular, recent literature strengthens the perception that diverse molecular signaling pathways, participating in the neuroprotective activity of the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), renders this natural compound as potential agent to reduce the risk of various neurodegenerative diseases. In the current review, we discuss the studies concerning the mechanisms of action implicated in EGCG-induced neuroprotection and discuss the vision to translate these findings into a lifestyle arena.