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Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082294" target="_blank" >RIV/00159816:_____/25:00082294 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14110/25:00140585

  • Result on the web

    <a href="https://onlinelibrary.wiley.com/doi/10.1111/cns.70192" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1111/cns.70192</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1111/cns.70192" target="_blank" >10.1111/cns.70192</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases

  • Original language description

    Introduction: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer&apos;s disease (AD) and Parkinson&apos;s disease (PD). USP30&apos;s orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration. Method: A systematic literature search was conducted in PubMed, Scopus, and Web of Science, selecting studies that investigated USP&apos;s function, inhibitor design, or therapeutic efficacy in AD and PD. Inclusion criteria encompassed mechanistic and preclinical/clinical data, while irrelevant or duplicate references were excluded. Extracted findings were synthesized narratively. Results: USP30 modulates interactions with translocase of outer mitochondrial membrane (TOM) 20, mitochondrial E3 ubiquitin protein ligase 1 (MUL1), and Parkin, thus harmonizing mitochondrial quality control. Emerging novel USP30 inhibitors, racemic phenylalanine derivatives, N-cyano pyrrolidine, and notably, benzosulphonamide class compounds, restore mitophagy, and reduce neurodegenerative phenotypes across diverse models with minimal off-target effects. Modulation of other USPs also influences neurodegenerative disease pathways, offering additional therapeutic avenues. Conclusions: In highlighting the nuanced regulation of mitophagy by USP30, this work heralds a shift toward more precise and effective treatments, paving the way for a new era in the clinical management of neurodegenerative disorders.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    <a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2025

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    CNS Neuroscience &amp; Therapeutics

  • ISSN

    1755-5930

  • e-ISSN

    1755-5949

  • Volume of the periodical

    31

  • Issue of the periodical within the volume

    1

  • Country of publishing house

    CN - CHINA

  • Number of pages

    25

  • Pages from-to

    "e70192"

  • UT code for WoS article

    001402852300001

  • EID of the result in the Scopus database