AI Article Synopsis
- Autophagy is a key cellular process that breaks down damaged materials and recycles nutrients, especially important during times of starvation.
- It plays a role in neurodegenerative diseases by removing harmful proteins and organelles, with increased autophagy showing promise in improving conditions in animal models.
- However, factors like aging and certain genetic mutations hinder autophagy, leading to a cycle where toxic proteins accumulate more, highlighting the need for research on autophagy's role in aging and neurodegenerative disorders for potential therapies.
Article Abstract
Autophagy is a conserved mechanism that degrades damaged or superfluous cellular contents and enables nutrient recycling under starvation conditions. Many neurodegeneration-associated proteins are autophagy substrates, and autophagy upregulation ameliorates disease in many animal models of neurodegeneration by enhancing the clearance of toxic proteins, proinflammatory molecules, and dysfunctional organelles. Autophagy inhibition also induces neuronal and glial senescence, a phenomenon that occurs with increasing age in non-diseased brains as well as in response to neurodegeneration-associated stresses. However, aging and many neurodegeneration-associated proteins and mutations impair autophagy. This creates a potentially detrimental feedback loop whereby the accumulation of these disease-associated proteins impairs their autophagic clearance, facilitating their further accumulation and aggregation. Thus, understanding how autophagy interacts with aging, senescence, and neurodegenerative diseases in a temporal, cellular, and genetic context is important for the future clinical application of autophagy-modulating therapies in aging and neurodegeneration.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuron.2024.09.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Alpha-synuclein knockout impairs melanoma development and alters DNA damage repair in the TG3 mouse model in a sex-dependent manner.
bioRxiv
December 2024
Department of Neurology and Jungers Center for Neurosciences Research, Oregon Health and Science University, Portland, OR, USA.
Strong evidence suggests links between Parkinson's Disease (PD) and melanoma, as studies have found that people with PD are at an increased risk of developing melanoma and those with melanoma are at increased risk of developing PD. Although these clinical associations are well-established, the cellular and molecular pathways linking these diseases are poorly understood. Recent studies have found a previously unrecognized role for the neurodegeneration-associated protein alpha-synuclein (αSyn) in melanoma; the overexpression of αSyn promotes melanoma cell proliferation and metastasis.
View Article and Find Full Text PDFPersistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.
Cell Host Microbe
December 2024
Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Munich, Neuherberg, Germany; Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; Koç University, School of Medicine, İstanbul, Turkey. Electronic address:
SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes.
View Article and Find Full Text PDFFrontal neurodegeneration associated with Frontal Assessment Battery in early Alzheimer's disease.
J Neurol Sci
December 2024
Department of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Background: The Frontal Assessment Battery (FAB) is widely used to assess executive dysfunction in patients with amnestic mild cognitive impairments due to Alzheimer's disease (aMCI-AD), but its neurobiological meaning is unclear. To elucidate this, we examined the relationship between the FAB score and three key imaging biomarkers: gray matter volume, amyloid-beta (Aβ) deposition, and glucose metabolism.
Methods: Twenty Aβ- and tau-positive aMCI-AD patients and age-matched controls underwent structural magnetic resonance imaging and positron emission tomography with [C]PiB and [F]FDG.
Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders.
Front Cell Neurosci
October 2024
Dr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United States.
Article Synopsis
- - The neurovascular unit (NVU) inflammation from glial cell activation and neuronal damage significantly contributes to neurodegenerative diseases, though the exact disease mechanisms are not fully understood.
- - Biomarkers like neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) can indicate the severity, progression, and treatment response in various brain disorders by assessing brain cell health and blood-brain barrier integrity.
- - Chronic inflammation is prevalent in age-related neurodegenerative diseases such as Alzheimer's and Parkinson's, and certain biomarkers may change years before disease onset, highlighting their potential for early detection and research into neurovascular pathologies.
Unraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer's disease.
Front Cell Neurosci
October 2024
Li Ka Shing Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Alzheimer's disease (AD) is marked by the gradual and age-related deterioration of nerve cells in the central nervous system. The histopathological features observed in the brain affected by AD are the aberrant buildup of extracellular and intracellular amyloid-β and the formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Axonal transport is a fundamental process for cargo movement along axons and relies on molecular motors like kinesins and dyneins.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!