ATM-deficient neural precursors develop senescence phenotype with disturbances in autophagy DOI Creative Commons
Piotr Sunderland, Justyna Augustyniak,

Jacek Lenart

et al.

Mechanisms of Ageing and Development, Journal Year: 2020, Volume and Issue: 190, P. 111296 - 111296

Published: July 1, 2020

ATM is a kinase involved in DNA damage response (DDR), regulation of to oxidative stress, autophagy and mitophagy. Mutations the gene humans result ataxi A-Telangiectasia disease (A-T) characterized by variety symptoms with neurodegeneration premature ageing among them. Since brain one most affected organs A-T, we have focused on senescence neural progenitor cells (NPCs) derived from A-T reprogrammed fibroblasts. Accordingly, NPCs obtained through differentiation iPSCs 5% oxygen possessed some features including increased activity SA-β-gal secretion IL6 IL8 comparison control NPCs. This phenotype NPC was accompanied elevated stress. exhibited impaired mitophagy lack chloroquine treatment. Additional sources stress like concentration (20 %) H2O2 respectively aggravated additionally disturbed process In both cases only reacted We conclude that may be responsible for impairment Our results point senescent as potential therapeutic target this disease.

Language: Английский

Cellular functions of the protein kinase ATM and their relevance to human disease DOI
Ji‐Hoon Lee, Tanya T. Paull

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(12), P. 796 - 814

Published: Aug. 24, 2021

Language: Английский

Citations

181
Chromosome instability syndromes DOI
A. Malcolm R. Taylor, Cynthia Rothblum‐Oviatt, Nathan A. Ellis

et al.

Nature Reviews Disease Primers, Journal Year: 2019, Volume and Issue: 5(1)

Published: Sept. 19, 2019

Language: Английский

Citations

178
Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia DOI Open Access
Mehdi Eshraghi, Aida Adlimoghaddam, Amir Mahmoodzadeh

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(7), P. 3330 - 3330

Published: March 24, 2021

Alzheimer's disease (AD) is a debilitating neurological disorder, and currently, there no cure for it. Several pathologic alterations have been described in the brain of AD patients, but ultimate causative mechanisms are still elusive. The classic hallmarks AD, including amyloid plaques (Aβ) tau tangles (tau), most studied features AD. Unfortunately, all efforts targeting these pathologies failed to show desired efficacy patients so far. Neuroinflammation impaired autophagy two other main known It has reported that exist long before emergence any clinical manifestation Microglia inflammatory cells considered by many researchers as next hope finding viable therapeutic target Interestingly, it appears mitophagy also changed Inside cells, inflammation interact bidirectional manner. In current review, we briefly discussed an overview on then provided comprehensive discussion role pathways microglia their involvement pathogenesis.

Language: Английский

Citations

111
Human cerebellar organoids with functional Purkinje cells DOI Creative Commons
Alexander Atamian, Marcella Birtele, Negar Hosseini

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(1), P. 39 - 51.e6

Published: Jan. 1, 2024

Language: Английский

Citations

35
The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force DOI Creative Commons
Marie Beaudin, Antoni Matilla‐Dueñas,

Bing-Weng Soong

et al.

The Cerebellum, Journal Year: 2019, Volume and Issue: 18(6), P. 1098 - 1125

Published: July 2, 2019

There is currently no accepted classification of autosomal recessive cerebellar ataxias, a group disorders characterized by important genetic heterogeneity and complex phenotypes. The objective this task force was to build consensus on the ataxias in order develop general approach patient presenting with ataxia, organize according clinical presentation, define field research identifying common pathogenic molecular mechanisms these disorders. work based previously published systematic scoping review literature that identified primarily motor dysfunction degeneration. regrouped 12 international ataxia experts who decided orientation specific issues. We 59 are classified as primary ataxias. For each disorders, we present geographical ethnical specificities along distinctive imagery features. These were organized pathophysiological classification, ataxia. also list 48 multisystem associated should be included differential diagnosis This result among panel experts, it promotes unified understanding for clinicians researchers.

Language: Английский

Citations

107
Modeling Neurodegenerative Disorders in Drosophila melanogaster DOI Open Access
Harris Bolus,

Kassi L. Crocker,

Grace Boekhoff‐Falk

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(9), P. 3055 - 3055

Published: April 26, 2020

Drosophila melanogaster provides a powerful genetic model system in which to investigate the molecular mechanisms underlying neurodegenerative diseases. In this review, we discuss recent progress modeling Alzheimer’s Disease, Parkinson’s Amyotrophic Lateral Sclerosis (ALS), Huntington’s Ataxia Telangiectasia, and neurodegeneration related mitochondrial dysfunction or traumatic brain injury. We close by discussing using models of neural regeneration how these are likely provide critical insights into future treatments for disorders.

Language: Английский

Citations

102
Autosomal Recessive Cerebellar Ataxias: Paving the Way toward Targeted Molecular Therapies DOI Creative Commons
Matthis Synofzik, Hélène Puccio, Fanny Mochel

et al.

Neuron, Journal Year: 2019, Volume and Issue: 101(4), P. 560 - 583

Published: Feb. 1, 2019

Language: Английский

Citations

101
Pexophagy: Molecular Mechanisms and Implications for Health and Diseases. DOI
Dong‐Hyung Cho, Yi Sak Kim,

Doo Sin Jo

et al.

PubMed, Journal Year: 2018, Volume and Issue: 41(1), P. 55 - 64

Published: Jan. 31, 2018

Autophagy is an intracellular degradation pathway for large protein aggregates and damaged organelles. Recent studies have indicated that autophagy targets cargoes through a selective called autophagy. Peroxisomes are dynamic organelles crucial health development. Pexophagy peroxisomes essential the maintenance of homeostasis peroxisomes, which necessary in prevention various peroxisome-related disorders. However, mechanisms by pexophagy regulated key players induce modulate largely unknown. In this review, we focus on our current understanding how induced regulated, adaptors involved mediating pexophagy. Furthermore, discuss findings roles physiological pathological responses, provide insight into clinical relevance regulation. Understanding interacts with biological functions will fundamental insights function facilitate development novel therapeutics against peroxisomal dysfunction-related diseases.

Language: Английский

Citations

77
Non-Coding RNAs and Resistance to Anticancer Drugs in Gastrointestinal Tumors DOI Creative Commons
Jens C. Hahne, Nicola Valeri

Frontiers in Oncology, Journal Year: 2018, Volume and Issue: 8

Published: June 18, 2018

Non-coding RNAs are important regulators of gene expression and transcription. It is well established that impaired non-coding RNA especially the one long microRNAs involved in a number pathological conditions including cancer. responsible for development resistance to anticancer treatments as they regulate drug resistance-related genes, affect intracellular concentrations, induce alternative signalling pathways, alter efficiency via blocking cell cycle regulation DNA damage response. Furthermore, can prevent therapeutic-induced death promote epithelial-mesenchymal transition elicit non-cell autonomous mechanisms resistance. In this review we summarise role different resulting (e.g. transport, metabolism, regulation, apoptotic cancer stem cells transition) context gastrointestinal cancers.

Language: Английский

Citations

64
Tetracycline Antibiotics Induce Host-Dependent Disease Tolerance to Infection DOI Creative Commons
Henrique G. Colaço, André Barros, Ana Neves‐Costa

et al.

Immunity, Journal Year: 2020, Volume and Issue: 54(1), P. 53 - 67.e7

Published: Oct. 14, 2020

Several classes of antibiotics have long been known to beneficial effects that cannot be explained strictly on the basis their capacity control infectious agent. Here, we report tetracycline antibiotics, which target mitoribosome, protected against sepsis without affecting pathogen load. Mechanistically, found mitochondrial inhibition protein synthesis perturbed electron transport chain (ETC) decreasing tissue damage in lung and increasing fatty acid oxidation glucocorticoid sensitivity liver. Using a liver-specific partial acute deletion Crif1, critical mitoribosomal component for synthesis, mice were sepsis, an observation was phenocopied by transient complex I ETC phenformin. Together, demonstrate mitoribosome-targeting are beyond antibacterial activity leading perturbation is mechanism induction disease tolerance.

Language: Английский

Citations

54