Exploring the Function of OPTN From Multiple Dimensions DOI
Yanan Guo, Yixiao Tian, Peng Xia

et al.

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(8)

Published: Dec. 1, 2024

ABSTRACT Autophagy is an essential intracellular degradation system responsible for delivering cytoplasmic components to lysosomes. Within this intricate process, optineurin (OPTN), autophagy receptor, has attracted extensive attention due its multifaceted roles in the process. OPTN regulated by various posttranslational modifications and actively participates numerous signaling pathways cellular processes. By exploring regulatory mechanism of modification, we can further understand critical role protein modification biological progress, such as autophagy. Additionally, implicated many human diseases, including rheumatoid arthritis, osteoporosis, infectious diseases. And delve into inflammatory clarify how it regulates diseases cancer. We aim enhance understanding OPTN's functions processes implications pathogenesis

Language: Английский

Ubiquitin E3 ligases assisted technologies in protein degradation: Sharing pathways in neurodegenerative disorders and cancer DOI
Aastha Kaushik,

Somya Parashar,

Rashmi K. Ambasta

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102279 - 102279

Published: March 22, 2024

Language: Английский

Citations

8
Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis DOI
Kiterie M. E. Faller, Helena Chaytow, Thomas H. Gillingwater

et al.

Nature Reviews Neurology, Journal Year: 2025, Volume and Issue: 21(2), P. 86 - 102

Published: Jan. 2, 2025

Language: Английский

Citations

1
DNA repair deficiencies and neurodegeneration DOI Creative Commons
Baptiste Ropert, Christian Gallrein, Björn Schumacher

et al.

DNA repair, Journal Year: 2024, Volume and Issue: 138, P. 103679 - 103679

Published: April 16, 2024

Neurodegenerative diseases are the second most prevalent cause of death in industrialized countries. Alzheimer's Disease is widespread and also acknowledged form dementia today. Together with Parkinson's they account for over 90 % cases neurodegenerative disorders caused by proteopathies. Far less known pathologies DNA repair deficiency syndromes. Such like Cockayne - or Werner Syndrome described as progeroid syndromes that premature ageing affected persons, there clear implications such neurologic dysfunction degeneration. In this review, we aim to draw attention on commonalities between proteopathy-associated neurodegeneration defects discuss how mitochondria implicated development both disorder classes. Furthermore, highlight nematodes a valuable indispensable model organism study conserved processes fast-forward manner.

Language: Английский

Citations

6
Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective DOI Open Access
Yu. V. Markitantova, V. N. Simirskii

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10776 - 10776

Published: June 28, 2023

The retinal pigment epithelium (RPE) performs a range of necessary functions within the neural layers retina and helps ensure vision. regulation pro-oxidative antioxidant processes is basis for maintaining RPE homeostasis preventing degenerative processes. Long-term stable changes in redox balance under influence endogenous or exogenous factors can lead to oxidative stress (OS) development number pathologies associated with dysfunction, eventually vision loss. Reparative autophagy, ubiquitin–proteasome utilization, repair damaged proteins, maintenance their conformational structure are important interrelated mechanisms defense system that protects against damage. Antioxidant protection cells realized as result activity specific transcription factors, large group enzymes, chaperone etc., which form many signaling pathways retina. Here, we discuss role key components (ADS) cellular response OS. Understanding interactions OS mediators ADS contributes formation ideas about subtle prospects experimental approaches restore functions.

Language: Английский

Citations

15
Recent advancements in the understanding of the alterations in mitochondrial biogenesis in Alzheimer’s disease DOI
Shreya Singh, Rakesh Kumar Singh

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Jan. 29, 2025

Language: Английский

Citations

0
Multi-omics-based phenotyping of AFG3L2-mutant lymphoblasts determines key factors of a pathophysiological interplay between mitochondrial vulnerability and neurodegeneration in spastic ataxia type 5 DOI Creative Commons

Menekse Oeztuerk,

Diran Herebıan,

Kale Dipali

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Feb. 20, 2025

Mitochondrial integrity is fundamental to cellular function, upheld by a network of proteases that regulate proteostasis and mitochondrial dynamics. Among these proteases, AFG3L2 critical due its roles in maintaining homeostasis, regulating protein quality, facilitating biogenesis. Mutations are implicated spectrum diseases, including spinocerebellar ataxia type 28 (SCA28) spastic 5 (SPAX5), as well other systemic conditions. This study employs multi-omics approach investigate the biochemical impact mutations immortalized lymphoblastoid cell lines derived from patient with biallelic variants leading (SPAX5). Our proteomic analysis revealed impairment, significant dysregulation proteins for cytoskeletal integrity, metabolism. Specifically, disruptions were observed dynamics calcium alongside downregulation key like COX11, copper chaperone complex IV assembly, NFU1, an iron-sulfur cluster linked paraparesis infection-related worsening. Lipidomic highlighted substantial alterations lipid composition, decreases sphingomyelins, phosphatidylethanolamine, phosphatidylcholine, reflecting metabolism membrane integrity. Metabolomic profiling did not reveal any findings. comprehensive investigation into loss functional elucidates pathophysiology extending beyond proteostasis, implicating wide array processes. The findings disturbances at multiple levels, contributing neurodegeneration through disrupted respiratory chain, altered homeostasis. underscores complexity SPAX5 importance approaches developing effective strategies address AFG3L2. data also highlight value cells tool pre-clinical testing research, offering detailed fingerprint enhances our understanding identifies potential areas further investigation.

Language: Английский

Citations

0
The neurotoxicity of pesticides: Implications for Parkinson's disease DOI Creative Commons
Leslie Amaral,

Mário Martins,

Manuela Côrte‐Real

et al.

Chemosphere, Journal Year: 2025, Volume and Issue: 377, P. 144348 - 144348

Published: April 9, 2025

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder worldwide, and no effective cure currently available. Neuropathologically, PD characterized by selective degeneration of dopaminergic neurons in substantia nigra accumulation alpha-synuclein (aSyn)-rich proteinaceous inclusions within surviving neurons. As a multifactorial disorder, approximately 85 % cases are sporadic with unknown etiology. Among many risk factors implicated PD, exposure to neurotoxic pesticides stands out as significant contributor. While effects still uncharacterized, it has already been shown that rotenone, paraquat, maneb, dieldrin affect critical cellular pathways, including mitochondrial proteasomal dysfunction, aSyn aggregation, autophagy dysregulation, disruption dopamine metabolism. With constant rise pesticide usage meet demands growing human population, environmental contamination subsequent development also increasing. This review explores molecular mechanisms which influences development, shedding light on their role pathogenesis highlighting need for preventative measures regulatory oversight mitigate these risks.

Language: Английский

Citations

0
Proteostasis imbalance: Unraveling protein aggregation in neurodegenerative diseases and emerging therapeutic strategies DOI

Chandrabose Selvaraj,

Periyasamy Vijayalakshmi,

Devangi Desai

et al.

Advances in protein chemistry and structural biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Roles of Mitochondrial Quality Control in the Pathogenesis of Atherosclerosis DOI Creative Commons

Zakareya M. Alsalman,

Qiongjun Zhu, Jiayi Hu

et al.

Cardiovascular Innovations and Applications, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 1, 2025

Mitochondrial quality control (MQC) mechanisms – including biogenesis, dynamics, mitophagy, proteostasis, the unfolded protein response, and mitochondrial-derived vesicles play critical roles in development of atherosclerosis. Dysregulation these processes can lead to mitochondrial dysfunction, subsequently initiation a pathological cascade characterized by oxidative stress, chronic inflammation, accumulation lipids within arterial walls. Specifically, ROS overproduction redox state imbalance are key molecular aspects that exacerbate damage, create self-perpetuating cycle cellular injury disease progression. Emerging therapeutic strategies targeting modulation MQC have promise attenuating atherosclerotic progression restoring balance fusion fission enhancing clearance damaged mitochondria, improving homeostasis. Advancing understanding regulators interaction networks pathways might facilitate precision-targeted therapies. However, substantial challenges persist translating insights into clinical applications. This review explores relationship between atherosclerosis, focusing on associated potential avenues for intervention.

Language: Английский

Citations

0
Age-Dependent Alterations in Platelet Mitochondrial Respiration DOI Creative Commons
Zdeněk Fišar, Jana Hroudová, Martina Zvěřová

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1564 - 1564

Published: May 28, 2023

Mitochondrial dysfunction is an important cellular hallmark of aging and neurodegeneration. Platelets are a useful model to study the systemic manifestations mitochondrial dysfunction. To evaluate age dependence parameters, citrate synthase activity, respiratory chain complex oxygen consumption kinetics were assessed. The effect cognitive impairment was examined by comparing parameters in healthy individuals those with neuropsychiatric disease. found significant negative slope age-dependence for both activity individual enzymes (citrate II) respiration intact platelets (routine respiration, maximum capacity electron transport system, rate after I inhibition). However, there no difference age-related changes between without impairment. These findings highlight potential measuring as means assess results indicate that drugs interventions targeting may have slow down or eliminate certain neurodegenerative processes. holds promise biomarker aging, irrespective degree

Language: Английский

Citations

9