Role of Mitochondria–ER Contact Sites in Mitophagy DOI Creative Commons

Alina Rühmkorf,

Angelika B. Harbauer

Biomolecules, Год журнала: 2023, Номер 13(8), С. 1198 - 1198

Опубликована: Июль 31, 2023

Mitochondria are often referred to as the "powerhouse" of cell. However, this organelle has many more functions than simply satisfying cells' metabolic needs. involved in calcium homeostasis and lipid metabolism, they also regulate apoptotic processes. Many these require contact with ER, which is mediated by several tether proteins located on respective organellar surfaces, enabling formation mitochondria-ER sites (MERCS). Upon damage, mitochondria produce reactive oxygen species (ROS) that can harm surrounding To circumvent toxicity maintain a functional pool healthy organelles, damaged excess be targeted for degradation via mitophagy, form selective autophagy. Defects tethers accumulation found neurodegenerative diseases, including Parkinson's disease amyotrophic lateral sclerosis, argues interplay between two organelles vital neuronal health. This review provides an overview different mechanisms mitochondrial quality control implicated proteins, novel perspective how MERCS mediating mitophagy upon damage.

Язык: Английский

Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities DOI Creative Commons

Marlene F. Schmidt,

Zhong Yan Gan, David Komander

и другие.

Cell Death and Differentiation, Год журнала: 2021, Номер 28(2), С. 570 - 590

Опубликована: Янв. 7, 2021

Abstract Neurodegenerative diseases are characterised by progressive damage to the nervous system including selective loss of vulnerable populations neurons leading motor symptoms and cognitive decline. Despite millions people being affected worldwide, there still no drugs that block neurodegenerative process stop or slow disease progression. Neuronal death in these is often linked misfolded proteins aggregate within brain (proteinopathies) as a result disease-related gene mutations abnormal protein homoeostasis. There two major degradation pathways rid cell unwanted prevent their accumulation maintain health cell: ubiquitin–proteasome autophagy–lysosomal pathway. Both degradative depend on modification targets with ubiquitin. Aging primary risk factor most Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis. With aging general reduction proteasomal autophagy, consequent increase potentially neurotoxic aggregates β-amyloid, tau, α-synuclein, SOD1 TDP-43. An over-looked yet component ubiquitin, implicating either an adaptive response toxic evidence dysregulated ubiquitin-mediated driving aggregation. In addition, non-degradative ubiquitin signalling critical for homoeostatic mechanisms fundamental neuronal function survival, mitochondrial homoeostasis, receptor trafficking DNA responses, whilst also playing role inflammatory processes. This review will discuss current understanding ubiquitin-dependent processes emergence target development much needed new treat disease.

Язык: Английский

Процитировано

280
The emerging mechanisms and functions of microautophagy DOI
Liming Wang, Daniel J. Klionsky, Han‐Ming Shen

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 24(3), С. 186 - 203

Опубликована: Сен. 12, 2022

Язык: Английский

Процитировано

250
The ubiquitin system: from cell signalling to disease biology and new therapeutic opportunities DOI Open Access
Rune Busk Damgaard

Cell Death and Differentiation, Год журнала: 2021, Номер 28(2), С. 423 - 426

Опубликована: Янв. 14, 2021

Язык: Английский

Процитировано

182
Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine DOI Open Access

Min-Rui Ding,

Yan-Jie Qu,

Bing Hu

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 152, С. 113208 - 113208

Опубликована: Май 31, 2022

This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), provide support further investigation on TCM its active ingredients.Literature survey was conducted using PubMed, Web Science, Google Scholar, CNKI, other databases, with "Alzheimer's disease," "traditional medicine," "medicinal herb," "Chinese "natural plant" as primary keywords.TCM could modulate related AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, PI3K/Akt/mTOR, well SIRT1 PPARα pathway. It regulate crosstalk between through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating system function, modulating autophagy, eventually improving cognitive impairment in patients AD.TCM be multilevel, multitargeted, multifaceted prevent treat AD. In-depth research prevention treatment new ideas exploring pathogenesis developing anti-AD drugs.

Язык: Английский

Процитировано

83
Neuroinflammation and neurodegeneration in Huntington’s disease: genetic hallmarks, role of metals and organophosphates DOI

Omkar Kumar Kunwar,

Shamsher Singh

Neurogenetics, Год журнала: 2025, Номер 26(1)

Опубликована: Янв. 17, 2025

Язык: Английский

Процитировано

2
Combating deleterious phase transitions in neurodegenerative disease DOI Creative Commons
April L. Darling, James Shorter

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2021, Номер 1868(5), С. 118984 - 118984

Опубликована: Фев. 5, 2021

Язык: Английский

Процитировано

80
Proteostasis in Parkinson's disease: Recent development and possible implication in diagnosis and therapeutics DOI

Amrita Kulkarni,

Preeti Kumari, Kamatham Pushpa Tryphena

и другие.

Ageing Research Reviews, Год журнала: 2022, Номер 84, С. 101816 - 101816

Опубликована: Дек. 6, 2022

Язык: Английский

Процитировано

39
Graphene Quantum Dots Modulate Stress Granule Assembly and Prevent Abnormal Phase Transition of Fused in Sarcoma Protein DOI
Hong Zhang, Jinge Gu, Yiling Zhang

и другие.

ACS Nano, Год журнала: 2023, Номер 17(11), С. 10129 - 10141

Опубликована: Май 19, 2023

Protein liquid–liquid phase separation (LLPS) plays a crucial role in mediating dynamic assembly of different membraneless organelles such as stress granules (SGs). Dysregulation protein LLPS leads to aberrant transition and amyloid aggregation which is closely associated with neurodegenerative diseases. In this study, we found that three types graphene quantum dots (GQDs) exhibit potent activity preventing SG formation promoting disassembly. We next demonstrate GQDs can directly interact the SGs-containing fused sarcoma (FUS), inhibit reverse FUS LLPS, prevent its abnormal transition. Moreover, display superior disaggregating preformed fibrils. Mechanistic study further demonstrates edge-site distinct binding affinity monomers fibrils, accounts for their activities modulating fibrillation. Our work reveals capability assembly, fibrillation sheds light on rational design effective modulators therapeutics application.

Язык: Английский

Процитировано

25
Lost in traffic: consequences of altered palmitoylation in neurodegeneration DOI Creative Commons
Firyal Ramzan, Fatima Abrar,

Gyana Gourab Mishra

и другие.

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Май 30, 2023

One of the first molecular events in neurodegenerative diseases, regardless etiology, is protein mislocalization. Protein mislocalization neurons often linked to proteostasis deficiencies leading build-up misfolded proteins and/or organelles that contributes cellular toxicity and cell death. By understanding how mislocalize neurons, we can develop novel therapeutics target earliest stages neurodegeneration. A critical mechanism regulating localization protein-lipid modification S-acylation, reversible addition fatty acids cysteine residues. S-acylation more commonly referred as S-palmitoylation or simply palmitoylation, which 16-carbon acid palmitate proteins. Like phosphorylation, palmitoylation highly dynamic tightly regulated by writers (i.e., palmitoyl acyltransferases) erasers depalmitoylating enzymes). The hydrophobic anchors membranes; thus, reversibility allows be re-directed from membranes based on local signaling factors. This particularly important nervous system, where axons (output projections) meters long. Any disturbance trafficking have dire consequences. Indeed, many involved diseases are palmitoylated, been identified palmitoyl-proteomic studies. It follows acyl transferase enzymes also implicated numerous diseases. In addition, work concert with mechanisms, like autophagy, affect health modifications, such acetylation, nitrosylation, ubiquitination, function turnover. Limited studies further revealed a sexually dimorphic pattern palmitoylation. Therefore, wide-reaching consequences

Язык: Английский

Процитировано

24
From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders DOI Creative Commons
Elisa Duranti, Chiara Villa

Biology, Год журнала: 2024, Номер 13(9), С. 719 - 719

Опубликована: Сен. 12, 2024

Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's (PD), primarily affect the central nervous system, leading to progressive neuronal loss motor cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe wasting as result of neuron degeneration, well alterations gene expression, protein aggregation, oxidative stress. Muscle atrophy mitochondrial dysfunction are observed AD, which may exacerbate decline due systemic metabolic dysregulation. PD patients exhibit fiber atrophy, altered composition, α-synuclein aggregation within cells, contributing symptoms progression. Systemic inflammation impaired degradation pathways common among disorders, highlighting key player Understanding muscle-related changes offers potential therapeutic avenues, such targeting function, reducing inflammation, promoting regeneration with exercise pharmacological interventions. This review emphasizes importance considering an integrative approach neurodegenerative research, both peripheral pathological mechanisms, order develop more effective treatments improve patient outcomes.

Язык: Английский

Процитировано

8