Brain Metabolomics: New Perspective on Neurodegenerative Disorders

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Pharmacology and Drug Metabolism".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 6055

Special Issue Editor


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Guest Editor
Department of Neurology, Georgetown University Medical Center, Washington, DC, USA
Interests: neurodegenerative diseases, PD, AD, ALS, LBD, etc.; blood brain barrier and angiogenesis; autopahgy; drug development

Special Issue Information

Dear colleagues,

This Special Issues broadly discusses protein clearance mechanisms via autophagy, the proteasome, and the lysosome in neurodegenerative diseases. It also will consider the direct effects on angiogenesis and the blood–brain barrier in health, disease and response to treatments. Inflammatory processes that are concurrent or independent of neurotoxic protein accumulation will also be considered. Papers concerning drug development as a strategy to treat neurodegeneration via manipulation of autophagy, the lysosome, and inflammation and restoration of the blood–brain barrier are particularly welcome.

Dr. Charbel Moussa
Guest Editor

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Keywords

  • autophagy
  • angiogenesis
  • new drug
  • drug developments
  • neuroinflammation
  • Alpha-synuclein
  • Tau
  • amyloid
  • TDP_43

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Published Papers (1 paper)

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Research

17 pages, 4201 KiB  
Article
Novel Ubiquitin Specific Protease-13 Inhibitors Alleviate Neurodegenerative Pathology
by Xiaoguang Liu, Kaluvu Balaraman, Ciarán C. Lynch, Michaeline Hebron, Christian Wolf and Charbel Moussa
Metabolites 2021, 11(9), 622; https://doi.org/10.3390/metabo11090622 - 15 Sep 2021
Cited by 14 | Viewed by 5345
Abstract
Ubiquitin Specific Protease-13 (USP13) promotes protein de-ubiquitination and is poorly understood in neurodegeneration. USP13 is upregulated in Alzheimer’s disease (AD) and Parkinson’s disease (PD), and USP13 knockdown via shRNA reduces neurotoxic proteins and increases proteasome activity in models of neurodegeneration. We synthesized novel [...] Read more.
Ubiquitin Specific Protease-13 (USP13) promotes protein de-ubiquitination and is poorly understood in neurodegeneration. USP13 is upregulated in Alzheimer’s disease (AD) and Parkinson’s disease (PD), and USP13 knockdown via shRNA reduces neurotoxic proteins and increases proteasome activity in models of neurodegeneration. We synthesized novel analogues of spautin-1 which is a non-specific USP13 inhibitor but unable to penetrate the brain. Our synthesized small molecule compounds are able to enter the brain, more potently inhibit USP13, and significantly reduce alpha-synuclein levels in vivo and in vitro. USP13 inhibition in transgenic mutant alpha-synuclein (A53T) mice increased the ubiquitination of alpha-synuclein and reduced its protein levels. The data suggest that novel USP13 inhibitors improve neurodegenerative pathology via antagonism of de-ubiquitination, thus alleviating neurotoxic protein burden in neurodegenerative diseases. Full article
(This article belongs to the Special Issue Brain Metabolomics: New Perspective on Neurodegenerative Disorders)
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