The Role of Endoproteolytic Processing in Neurodegeneration

Wilson, Cornelia M.; Mushtaq, Gohar; Kamal, Mohammad Amjad; Terro, Faraj

doi:10.2174/1871527315666160922163511

Cited by 2 publications

(2 citation statements)

References 80 publications

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“…HTT protein is commonly distributed in the CNS and other non-neuronal tissues. It spreads across the compartments, and in human, HTT protein is a large protein with a molecular weight of 350 kDa (3144 aa) [ 176 ]. Expansions of CAG may mediate neurodegeneration through an abnormal expansion of polyQ, and an inductive Huntington’s disease (HD) transgenic mouse model was created with the first HTT exon (HTTex1), which includes the expansion of the CAG.…”

Section: Role Of Evs In Neurodegenerative Diseasesmentioning

confidence: 99%

Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

Belkozhayev

Al-Yozbaki

George

et al. 2022

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There are different modalities of intercellular communication governed by cellular homeostasis. In this review, we will explore one of these forms of communication called extracellular vesicles (EVs). These vesicles are released by all cells in the body and are heterogeneous in nature. The primary function of EVs is to share information through their cargo consisting of proteins, lipids and nucleic acids (mRNA, miRNA, dsDNA etc.) with other cells, which have a direct consequence on their microenvironment. We will focus on the role of EVs of mesenchymal stem cells (MSCs) in the nervous system and how these participate in intercellular communication to maintain physiological function and provide neuroprotection. However, deregulation of this same communication system could play a role in several neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, multiple sclerosis, prion disease and Huntington’s disease. The release of EVs from a cell provides crucial information to what is happening inside the cell and thus could be used in diagnostics and therapy. We will discuss and explore new avenues for the clinical applications of using engineered MSC-EVs and their potential therapeutic benefit in treating neurodegenerative diseases.

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Section: Role Of Evs In Neurodegenerative Diseasesmentioning

confidence: 99%

Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

Belkozhayev

Al-Yozbaki

George

et al. 2022

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“…Proteolysis is central to the degradation of misfolded proteins by the ubiquitin‐proteasome system and autophagy, both driven through minimotifs and central to NDs [164]. The inherent role of endoproteolysis in neurodegeneration was founded in the familial genetics of APP processing to β‐amyloid and was recently reviewed [165]. In early onset AD, β‐secretase and γ‐secretase cleave APP‐producing amyloidogenic Aβ 40 or Aβ 42 [87,166,167].…”

Section: Types Of Minimotifs In Neurodegenerative Diseasesmentioning

confidence: 99%

Minimotifs dysfunction is pervasive in neurodegenerative disorders

Sharma

Young²,

Chen

et al. 2018

A&D Transl Res & Clin Interv

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Minimotifs are modular contiguous peptide sequences in proteins that are important for posttranslational modifications, binding to other molecules, and trafficking to specific subcellular compartments. Some molecular functions of proteins in cellular pathways can be predicted from minimotif consensus sequences identified through experimentation. While a role for minimotifs in regulating signal transduction and gene regulation during disease pathogenesis (such as infectious diseases and cancer) is established, the therapeutic use of minimotif mimetic drugs is limited. In this review, we discuss a general theme identifying a pervasive role of minimotifs in the pathomechanism of neurodegenerative diseases. Beyond their longstanding history in the genetics of familial neurodegeneration, minimotifs are also major players in neurotoxic protein aggregation, aberrant protein trafficking, and epigenetic regulation. Generalizing the importance of minimotifs in neurodegenerative diseases offers a new perspective for the future study of neurodegenerative mechanisms and the investigation of new therapeutics.

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The Role of Endoproteolytic Processing in Neurodegeneration

Cited by 2 publications

References 80 publications

Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

Minimotifs dysfunction is pervasive in neurodegenerative disorders

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