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Articles on Neurodegenerative Diseases

Published on: 30 Mar 2022 Viewed: 260

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles about Neurodegenerative Diseases.

Title: The neuroprotective effects of intermittent fasting on brain aging and neurodegenerative diseases via regulating mitochondrial function
Authors: Yihang Zhao,Mengzhen Jia,Weixuan Chen,Zhigang Liu
Type: Review Article
Highlights:
●Intermittent fasting (IF) has benefits to brain aging and neurodegeneration.
●IF may protect mitochondrial function in brain, liver and skeletal muscle.
●IF may enhance mitochondrial biogenesis and regulate mitochondrial dynamics.
●SIRT1 and SIRT3 are regulators involved in IF modulating mitochondrial function.
Abstract:
Intermittent fasting (IF) has been studied for its effects on lifespan and the prevention or delay of age-related diseases upon the regulation of metabolic pathways. Mitochondria participate in key metabolic pathways and play important roles in maintaining intracellular signaling networks that modulate various cellular functions. Mitochondrial dysfunction has been described as an early feature of brain aging and neurodegeneration. Although IF has been shown to prevent brain aging and neurodegeneration, the mechanism is still unclear. This review focuses on the mechanisms by which IF improves mitochondrial function, which plays a central role in brain aging and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The cellular and molecular mechanisms of IF in brain aging and neurodegeneration involve activation of adaptive cellular stress responses and signaling- and transcriptional pathways, thereby enhancing mitochondrial function, by promoting energy metabolism and reducing oxidant production.
Access this article: https://doi.org/10.1016/j.freeradbiomed.2022.02.021


Title: Unearthing the mechanisms of age-related neurodegenerative disease using Caenorhabditis elegans
Authors: Ashley N. Hayden, Emily J. Leptich, Rachel N. Arey
Type: Review Article
Highlights:
●We highlight the utility of C. elegans as a neurodegenerative disease model.
●Neurodegenerative disease can be modeled at multiple levels – from genes to phenotypes.
●Genetic techniques in the worm are especially powerful for rapidly developing new disease models.
Abstract:
As human life expectancy increases, neurodegenerative diseases present a growing public health threat, for which there are currently few effective treatments. There is an urgent need to understand the molecular and genetic underpinnings of these disorders so new therapeutic targets can be identified. Here we present the argument that the simple nematode worm Caenorhabditis elegans is a powerful tool to rapidly study neurodegenerative disorders due to their short lifespan and vast array of genetic tools, which can be combined with characterization of conserved neuronal processes and behavior orthologous to those disrupted in human disease. We review how pre-existing C. elegans models provide insight into human neurological disease as well as an overview of current tools available to study neurodegenerative diseases in the worm, with an emphasis on genetics and behavior. We also discuss open questions that C. elegans may be particularly well suited for in future studies and how worms will be a valuable preclinical model to better understand these devastating neurological disorders.
Access this article: https://doi.org/10.1016/j.cbpa.2022.111166


Title: Role of nutraceuticals on neurodegenerative diseases: neuroprotective and immunomodulant activity
Authors: Angelo Fumia, Nicola Cicero, Marco Gitto, Noemi Nicosia, Alessio Alesci
Type: Review Article
Abstract:
Neurodegeneration is a degenerative process characterized by the progressive loss of the structure and function of neurons that involves several immune cells. It is the primary cause of dementia and other several syndromes, known as neurodegenerative diseases. These disorders are age-related and it is estimated that by 2040 there will be approximately 81.1 million people suffering from these diseases. In addition to the traditional pharmacological therapy, in recent years nutraceuticals, naturally based compounds with a broad spectrum of biological effects: anti-aging, antioxidants, hypoglycaemic, hypocholesterolemic, anticancer, anxiolytic, antidepressant, etc., assumed an important role in counteracting these pathologies. In particular, several compounds such as astaxanthin, baicalein, glycyrrhizin, St. John's wort, and Ginkgo biloba L. extracts show particular neuroprotective and immunomodulatory abilities, involving several immune cells and some neurotransmitters that play a critical role in neurodegeneration, making them particularly useful in improving the symptoms and progression of neurodegenerative diseases.
Access this article: https://doi.org/10.1080/14786419.2021.2020265


Title: Autophagy system as a potential therapeutic target for neurodegenerative diseases
Authors: Mengying Cui, Tamotsu Yoshimori, Shuhei Nakamura
Type: Review Article
Highlights:
●In neurodegenerative disease, autophagy-lysosome pathway is impaired.
●Neurodegenerative disease-related mutant proteins affect multiple steps of autophagy.
●Impairment of autophagy results in neurodegenerative disease, while activation of autophagy ameliorates neurodegeneration.
●Upregulation of autophagy in neurons to combat disorders that involve protein aggregation and dysfunctional organelles is a promising therapeutic strategy for neurodegenerative disease.
Abstract:
Autophagy is an evolutionally conserved process by which cytoplasmic contents including protein aggregates and damaged organelles such as mitochondria and lysosomes, are sequestered by double-membrane structure, autophagosomes, and delivered to the lysosomes for degradation. Recently, considerable efforts have been made to reveal the role of autophagy in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Huntington's disease. Impairment of autophagy aggravates the accumulation of misfolded protein and damaged organelles in neurons, while sufficient autophagic activity reduces such accumulation in nervous system and ameliorates the pathology. Here we summarize recent progress regarding the role of autophagy in several neurodegenerative diseases and the potential autophagy-associated therapies for them.
Access this article: https://doi.org/10.1016/j.neuint.2022.105308


Title: Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases
Authors: Andrew Chang, Xinyu Xiang, Jing Wang, Carolyn Lee, Tamta Arakhamia, Marija Simjanoska, Chi Wang, Yari Carlomagno, Guoan Zhang, Shikhar Dhingra, Manon Thierry, Jolien Perneel, Bavo Heeman, Lauren M. Forgrave, Michael DeTure, Mari L. DeMarco, Casey N. Cook, Rosa Rademakers, Dennis W. Dickson, Leonard Petrucelli, Michael H.B. Stowell, Ian R.A. Mackenzie, Anthony W.P. Fitzpatrick
Type: Article
Highlights:
●Cryo-EM structures of brain-derived TMEM106B fibrils from neurodegenerative diseases
●Endolysosomal membrane protein TMEM106B C-terminal fragment forms amyloid fibrils
●TMEM106B fibrillization is widespread among diverse neurodegenerative proteinopathies
●Identification of fibrillization pathway potentially implicated in neurodegeneration
Summary:
Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 Å from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration.
Access this article: https://doi.org/10.1016/j.cell.2022.02.026


Title: HnRNP K mislocalisation in neurons of the dentate nucleus is a novel neuropathological feature of neurodegenerative disease and ageing
Authors: Sidhu, Rahul; Gatt, Ariana; Fratta, Pietro; Lashley, Tammaryn; Bampton, Alexander
Type: Article
Abstract:
Nuclear depletion and cytoplasmic mislocalisation of the RNA-binding protein heterogeneous ribonucleoprotein K (hnRNP K) within pyramidal neurons of the frontal cortex have been shown to be a common neuropathological feature in frontotemporal lobar degeneration (FTLD) and elderly control brain. Here, we describe a second neuronal subtype vulnerable to mislocalisation within the dentate nucleus of the cerebellum. In contrast to neurons within the cerebellar cortex that typically exhibited normal, nuclear staining, many neurons of the dentate nucleus exhibited striking mislocalisation of hnRNP K to the cytoplasm within neurodegenerative disease brain. Mislocalisation frequency in this region was found to be significantly higher in both FTLD-TDP A and Alzheimer's disease (AD) brain than in age-matched controls. However, within control (but not disease) subjects, mislocalisation frequency was significantly associated with age-at-death with more elderly controls typically exhibiting greater levels of the pathology. This study provides further evidence for hnRNP K mislocalisation being a more anatomically diverse pathology than previously thought and suggests that potential dysfunction of the protein may be more broadly relevant to the fields of neurodegeneration and ageing.
Access this article: https://doi.org/10.1111/nan.12793

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