Published: Aug. 13, 2024
Language: Английский
Biogerontology, Journal Year: 2023, Volume and Issue: 24(5), P. 609 - 662
Published: July 30, 2023
Language: Английский
Citations
80
Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)
Published: May 29, 2024
Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.
Language: Английский
Citations
32
Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(5), P. 998 - 1005
Published: Sept. 22, 2023
Mitochondria are critical cellular energy resources and central to the life of neuron. Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery maintain mitochondrial quality control homeostasis. Mature neurons postmitotic consume substantial energy, thus require highly efficient mitophagy pathways turn over mitochondria. Recent evidence indicates that is pivotal pathogenesis neurological diseases. However, more work needed study pathway components as potential therapeutic targets. In this review, we briefly discuss characteristics nonselective autophagy selective autophagy, including ERphagy, aggrephagy, mitophagy. We then introduce mechanisms Parkin-dependent Parkin-independent under physiological conditions. Next, summarize diverse repertoire membrane receptors phospholipids mediate Importantly, review role in neurodegenerative diseases Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis. Last, recent studies considering a target for treating Together, our may provide novel views better understand roles disease pathogenesis.
Language: Английский
Citations
23
Neurological Sciences, Journal Year: 2024, Volume and Issue: 45(9), P. 4121 - 4131
Published: April 27, 2024
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons severe skeletal muscle atrophy. The etiology ALS linked to muscle, which can activate retrograde signaling cascade destroys neurons. This why satellite cells mitochondria play crucial role health performance muscles. review presents current knowledge on involvement mitochondrial dysfunction, atrophy, cells, junction (NMJ) ALS. It also discusses therapeutic strategies, including exercise, drugs, stem gene therapy, prospective use transplantation as viable strategy.
Language: Английский
Citations
10
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16833 - 16833
Published: Nov. 27, 2023
Amyotrophic lateral sclerosis (ALS) is a fatal multisystem disease characterized by progressive death of motor neurons, loss muscle mass, and impaired energy metabolism. More than 40 genes are now known to be associated with ALS, which together account for the majority familial forms ALS only 10% sporadic cases. To date, there no consensus on pathogenesis makes it difficult develop effective therapy. Accumulating evidence indicates that mitochondria, play an important role in cellular homeostasis, earliest targets abnormalities their structure functions contribute development bioenergetic stress progression. Mitochondria highly dynamic organelles, stability maintained through number key regulatory pathways. Mitochondrial homeostasis dynamically regulated via mitochondrial biogenesis, clearance, fission/fusion, trafficking; however, processes providing “quality control” distribution organelles prone dysregulation ALS. Here, we systematically summarized changes turnover, dynamics, calcium alterations transport provide in-depth insights into progression pathways, may have significant impact current symptomatic therapies personalized treatment programs patients
Language: Английский
Citations
17
Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17
Published: June 21, 2023
Translocator protein (TSPO), a 18 kDa found in the outer mitochondrial membrane, has historically been associated with transport of cholesterol highly steroidogenic tissues though it is all cells throughout mammalian body. TSPO also molecular transport, oxidative stress, apoptosis, and energy metabolism. levels are typically low central nervous system (CNS), but significant upregulation observed activated microglia during neuroinflammation. However, there few specific regions that have reported to higher than rest brain under normal conditions. These include dentate gyrus hippocampus, olfactory bulb, subventricular zone, choroid plexus, cerebellum. areas adult neurogenesis, yet no explanation TSPO’s function these cells. Current studies investigated role neuron degeneration, lifecycle remains be elucidated. This review aims discuss known functions its potential neurons within CNS.
Language: Английский
Citations
14
Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: 35(5), P. 549 - 563
Published: Feb. 21, 2024
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN LMN) innervating the muscles of trunk, extremities, head, neck face in cerebrum, brain stem spinal cord, results progressive weakness, atrophy fasciculation muscle innervated by related UMN LMN, accompanying with pathological signs leaded cortical tract lesion. The pathogenesis about ALS not fully understood, no specific drugs are available to cure prevent progression this at present. In review, we reviewed structure associated functions copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 crucial ALS, outline pathogenic mechanisms that have been identified recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative axonal transport disruption, prion-like propagation, non-cytologic toxicity glial cells. This review will help us deeply understand current field ALS.
Language: Английский
Citations
4
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3251 - 3251
Published: March 13, 2024
Amyotrophic Lateral Sclerosis (ALS) is considered the prototype of motor neuron disease, characterized by loss and muscle waste. A well-established pathogenic hallmark ALS mitochondrial failure, leading to bioenergetic deficits. So far, pharmacological interventions for disease have proven ineffective. Trimetazidine (TMZ) described as a metabolic modulator acting on different cellular pathways. Its efficacy in enhancing muscular cardiovascular performance has been widely described, although its molecular target remains elusive. We addressed mechanisms underlying TMZ action neuronal experimental paradigms. To this aim, we treated murine SOD1G93A-model-derived primary cultures cortical spinal enriched neurons, well motor-neuron-like cell line overexpressing SOD1G93A, with TMZ. first profile cultures, demonstrating significant dysfunction that reversed acute treatments. then investigated effect promoting autophagy processes impact morphology. Finally, demonstrated effectiveness terms functionality ALS-rpatient-derived peripheral blood mononuclear cells (PBMCs). In summary, our results emphasize concept targeting may represent an effective therapeutic strategy ALS. The findings demonstrate enhances activating processes, particularly mitophagy. Although further investigations are needed elucidate precise pathways involved, these hold critical implications development more specific derivatives treatment.
Language: Английский
Citations
4
Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1294 - 1294
Published: June 11, 2024
Amyotrophic lateral sclerosis is a severe neurodegenerative disease whose exact cause still unclear. Currently, research attention turning to the mitochondrion as critical organelle of energy metabolism. Current knowledge sufficient confirm involvement mitochondria in pathophysiology disease, since are involved many processes cell; however, mechanism We used peripheral blood mononuclear cells isolated from whole fresh patients with amyotrophic for measurement and matched an age- sex-matched set healthy subjects. The group consisted examined diagnosed at neurological clinic University Hospital Martin. controls individuals who were actively searched, selected on basis age sex. 26 sporadic forms ALS (13 women, 13 men), based definitive criteria El Escorial. average was 54 years, 56 years. high-resolution O2K respirometry method, Oxygraph-2k, measure mitochondrial respiration. Basal respiration lower by 29.48%, pyruvate-stimulated (respiratory chain complex I) 29.26%, maximal respiratory capacity 28.15%. decrease succinate-stimulated II) 26.91%. Our data changes patients, manifested reduced function I II chain. These defects enough this disease’s hypothesized damage. Therefore, interest future should be directed towards deeper understanding complexes disease. This could develop new biomarkers diagnostics subsequent therapeutic interventions.
Language: Английский
Citations
4
Journal of Cellular Biochemistry, Journal Year: 2023, Volume and Issue: 124(10), P. 1466 - 1485
Published: Oct. 1, 2023
Abstract With the decline in number of new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infections, World Health Organization announced end SARS‐CoV‐2 pandemic. However, repercussions this viral pandemic may remain with us for a longer period time, as it has remodeled lives humankind many ways, including social and economic. Of course, its most important on human health level. Long‐coronavirus disease (COVID) or post‐COVID is state which we do not have concrete definition, specific international classification diseases Code, clear diagnostic tools, well‐known effective cures yet. In second article from Intrinsic Factors behind long‐COVID Series, try to link symptoms their causes, starting nervous system. Extracellular vesicles (ECVs) play very complex ramified roles bodies both healthy not‐healthy individuals. ECVs facilitate entry bioactive molecules pathogens into tissues cells system across blood–brain barrier. Based size, quantity, quality cargo, are directly proportional pathological condition severity through intertwined mechanisms that evoke inflammatory immune responses typically accompanied by over variable time periods according type these symptoms.
Language: Английский
Citations
10