Research Topic

Ubiquitin and the Brain: Roles of Proteolysis in the Normal and Abnormal Nervous System

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Proteolysis by the ubiquitin-proteasome pathway (UPP) is now widely recognized as a major molecular mechanism playing a role in numerous normal functions of the nervous system as well as in malfunctions of the brain in several neurodegenerative diseases. In the UPP, attachment of a small protein, ubiquitin, ...

Proteolysis by the ubiquitin-proteasome pathway (UPP) is now widely recognized as a major molecular mechanism playing a role in numerous normal functions of the nervous system as well as in malfunctions of the brain in several neurodegenerative diseases. In the UPP, attachment of a small protein, ubiquitin, tags the substrates for degradation by a multi-subunit complex called the proteasome. Linkage of ubiquitin to protein substrates is highly specific and occurs through a series of well-orchestrated enzymatic steps. Protein degradation has key functions in the nervous system including fine-tuning of synaptic connections during development and synaptic plasticity in the adult organism. Among the diseases connected to the UPP are neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Amyotrophic Lateral Sclerosis. Perturbation in the UPP is also believed to play a causative role in mental disorders such as Angelman syndrome.
Many questions pertaining to the UPP in the nervous system remain unanswered. How is the UPP-mediated degradation regulated spatially and temporally in neurons? What is the role of local protein degradation? How does the interplay between proteolysis and protein synthesis affect synaptic plasticity and memory? Do perturbations in the UPP have a role in the pathology of neurodegenerative diseases?
To cover this rapidly expanding area of research, this Research Topic will cover wide-ranging topics on normal physiological functions of the UPP in the nervous system and the roles of proteolysis in neurodegenerative diseases. Manuscripts from studies on any model system (invertebrate and vertebrate animal models, isolated neurons or neuronal cell lines, human subjects and post-mortem human brain) are welcome. Since we like to keep the topic as broad as possible, we encourage authors to submit studies on other proteins in the ubiquitin family such as the small ubiquitin-like modifier (SUMO). In terms of approaches also the Research Topic will be broad in scope and thus we expect to include papers on investigations carried out at molecular, cellular and behavioral levels.
For this Research Topic , we welcome contributions in a variety of formats, such as original research reports, mini review, review and methods.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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