The Decline of Mitophagy in Age-Related Neurodegenerative Conditions

Mitochondria are the power plants of the cell. A herd of these bacteria-like organelles in every cell manufacture the chemical energy store molecules that are used to power cellular processes. Mitochondrial function declines with age throughout the body. Evidence suggests that this is due to changes in mitochondrial dynamics that inhibit the quality control mechanisms of mitophagy that are responsible for recycling worn and damaged mitochondria. This loss of miochondrial function is well known to contribute to the progression of neurodegenerative conditions, as the brain is an energy-hungry organ, making this an important aspect of aging to target for reversal. Mitochondrial health is vital for cellular and organismal homeostasis, and mitochondrial defects have long been linked to the pathogenesis of neurodegenerative diseases such as Alzheimer's, Parkinson's, ALS, Huntington's, and others. However, it is still unclear whether cellular mechanisms required for the maintenance of mitochondrial integrity and function are deficient in these diseases, thus exacerbating mitochondrial pathology. The quality control of mitochondria involves multiple levels of strategies to protect against mitochondrial damage and maintain a healthy mitochondrial population within cells. In neurons, mitophagy serves as a major pathway of the quality control mechanisms for the removal of aged and defective mitochondria through lysosomal proteolysis. The molecular and cellular mechanisms that g...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ino A Abstract Neurodegenerative diseases affect millions of people around the world. Several studies point out caspase-3 as a key player in the development and progression of neurological disorders including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's and Huntington's diseases. Furthermore, oxidative stress and mitochondrial dysfunction plays an important role in neurodegenerative pathologies leading to neuronal damage and cell death. Pharmacological properties of nitrones such as free radical trapping and neuroprotection has been previously described. In the present work, we have assessed ten non-cyt...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Abstract The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as to the injury and death of neurons due to an excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in a dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. De...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
This study supports the hypotheses that abnormal redox signalling in muscle contributes to altered proteostasis and motor impairment in HD, and that redox interventions can improve muscle performance, highlighting the importance of peripheral therapeutics in HD. PMID: 31751762 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Tabassum R, Jeong NY Abstract Oxidative phosphorylation is a source of energy production by which many cells satisfy their energy requirements. Endogenous reactive oxygen species (ROS) are by-products of oxidative phosphorylation. ROS are formed due to the inefficiency of oxidative phosphorylation, and lead to oxidative stress that affects mitochondrial metabolism. Chronic oxidative stress contributes to the onset of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The immediate consequences of oxidat...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
Publication date: Available online 31 October 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Kevin McAvoy, Hibiki KawamataAbstractMitochondria play essential metabolic roles in neural cells. Mitochondrial dysfunction has profound effects on the brain. In primary mitochondrial diseases, mutations that impair specific oxidative phosphorylation (OXPHOS) proteins or OXPHOS assembly factors lead to isolated biochemical defects and a heterogeneous group of clinical phenotypes, including mitochondrial encephalopathies. A broader defect of OXPHOS function, due to mutations in proteins involved in mitochondrial DNA maint...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
Publication date: Available online 17 October 2019Source: Molecular Aspects of MedicineAuthor(s): J.V. Cabral-Costa, A.J. KowaltowskiAbstractThe brain is highly dependent on mitochondrial energy metabolism. As a result, mitochondrial dysfunction is a central aspect of many adult-onset neurological diseases, including stroke, ALS, Alzheimer's, Huntington's, and Parkinson's diseases. We review here how different mitochondrial functions, including oxidative phosphorylation, mitochondrial dynamics, oxidant generation, cell death regulation, Ca2+ homeostasis, and proteostasis are involved in these disorders.
Source: Molecular Aspects of Medicine - Category: Molecular Biology Source Type: research
Abstract NAD+ is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD+-dependent enzymes are involved in synaptic plasticity and neuronal stress resistance. Here, we review emerging findings that reveal key roles for NAD+ and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer's, Parkinson's, and Huntington diseases, and amyotrophic lateral sclerosis. Advances in underst...
Source: Cell Metabolism - Category: Cytology Authors: Tags: Cell Metab Source Type: research
Role of PGC-1α in Mitochondrial Quality Control in Neurodegenerative Diseases. Neurochem Res. 2019 Aug 13;: Authors: Zhang Q, Lei YH, Zhou JP, Hou YY, Wan Z, Wang HL, Meng H Abstract As one of the major cell organelles responsible for ATP production, it is important that neurons maintain mitochondria with structural and functional integrity; this is especially true for neurons with high metabolic requirements. When mitochondrial damage occurs, mitochondria are able to maintain a steady state of functioning through molecular and organellar quality control, thus ensuring neuronal function. And whe...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
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