Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 327 - 327

Published: Jan. 31, 2025

Neurodegenerative disease (ND) refers to the progressive loss and morphological abnormalities of neurons in central nervous system (CNS) or peripheral (PNS). Examples neurodegenerative diseases include Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS). Recent studies have shown that mitochondria play a broad role cell signaling, immune response, metabolic regulation. For example, mitochondrial dysfunction is closely associated with onset progression variety diseases, including ND, cardiovascular diabetes, cancer. The energy metabolism, imbalance dynamics, abnormal mitophagy can lead homeostasis, which induce pathological reactions such as oxidative stress, apoptosis, inflammation, damage system, participate occurrence development degenerative AD, PD, ALS. In this paper, latest research progress subject detailed. mechanisms mitophagy-mediated ND are reviewed from perspectives β-amyloid (Aβ) accumulation, dopamine neuron damage, superoxide dismutase 1 (SOD1) mutation. Based on mechanism research, new ideas methods for treatment prevention proposed.

Language: Английский

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Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range substrates. KLHL proteins critical maintaining proteostasis in variety tissues and mutated human diseases, including cancer, neurodegeneration, familial hyperkalemic hypertension. However, regulation remains incompletely understood. Previously, we reported that two members, KEAP1 gigaxonin, regulated by O-linked β- N -acetylglucosamine (O-GlcNAc), an intracellular form glycosylation. Interestingly, some ubiquitination targets gigaxonin themselves also O-GlcNAcylated, suggesting multi-level control this post-translational modification may influence many pathways. To test hypothesis, examined KLHL3, which ubiquitinates with-no-lysine (WNK) kinases to modulate downstream ion channel activity. Our biochemical glycoproteomic data demonstrate KLHL3 all four WNK (WNK1-4) O-GlcNAcylated. Moreover, our results suggest O-GlcNAcylation affects WNK4 function both osmolarity ferroptosis, with potential implications ranging from blood pressure neuronal health survival. This work demonstrates functional KLHL3/WNK axis supports broader model O-GlcNAc serving as general regulator signaling proteostasis.

Language: Английский

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Role of Cell Deaths in Human Disabilities

Published: Jan. 1, 2025

Language: Английский

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Phospholipids and peroxisomes in ferroptosis: the therapeutic target of acupuncture regulating vascular cognitive impairment and dementia

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: April 29, 2025

Ferroptosis, since its conceptualization in 2012, has witnessed an exponential growth research interest over recent years. It is regulated by various cellular metabolic pathways during chronic cerebral ischemia and hypoxia, including reactive oxygen species (ROS) generation, iron accumulation, abnormalities glutathione metabolism, disruptions lipid glucose metabolism. With the deepening widespread research, ferroptosis emerged as a critical pathway pathogenesis of vascular cognitive impairment dementia (VCID). This unique cell death caused iron-dependent phospholipid peroxidation strongly related to VICD. We examine impact composition on neuronal susceptibility ferroptosis, with particular focus role polyunsaturated fatty acids (PUFAs) this process. Intriguingly, peroxisomes, key regulators metabolism oxidative stress, influence cells through synthesis plasmalogens other species. In Review, we provide analysis current molecular mechanisms regulatory networks acupuncture for potential functions peroxisomal neuroprotective effects VCID, together therapeutic targeting. As such, highlights theoretical basis application VCID multi-target regulation ferroptosis. review underscores non-pharmacological approach offering new insights into modulating associated neuroprotection.

Language: Английский

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Thyroid-associated ophthalmopathy and ferroptosis: a review of pathological mechanisms and therapeutic strategies

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 6, 2024

Thyroid-associated ophthalmopathy (TAO) is an inflammatory orbital disease associated with autoimmune thyroid disorders. Owing to the ambiguous nature of pathogenesis, contemporary pharmacological treatment strategies predominantly involve use glucocorticoids and immunosuppressants. However, adverse effects these agents in clinical practice necessitate further investigation into disease's pathogenesis identification novel therapeutic targets interventions. Recent studies suggest that ferroptosis, a form regulated cell death, may play role TAO pathogenesis. This review aims explore involvement ferroptosis evaluate its potential as target. Key topics include epidemiology, manifestations, pathophysiology TAO, along molecular mechanisms ferroptosis. Evidence supporting implications targeting this pathway are also discussed, alongside challenges future directions emerging research area.

Language: Английский

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Transcranial alternating current stimulation inhibits ferroptosis and promotes functional recovery in spinal cord injury via the cGMP-PKG signalling pathway

Life Sciences, Journal Year: 2024, Volume and Issue: unknown, P. 123341 - 123341

Published: Dec. 1, 2024

Language: Английский

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