The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy

Megan Dubowsky; Frances Theunissen; Jillian M. Carr; Mary-Louise Rogers

doi:10.1007/s12035-023-03472-y

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The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy

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The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy

Megan Dubowsky, Frances Theunissen, Jillian M. Carr and Mary-Louise Rogers

Molecular neurobiology, Vol.60(11), pp.6330-6345

2023

DOI: https://doi.org/10.1007/s12035-023-03472-y

PMID: 37450244

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Abstract

Life Sciences & Biomedicine

Neurosciences

Neurosciences & Neurology

Science & Technology

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurological disorder, characterised by the death of upper and lower motor neurons. The aetiology of ALS remains unknown, and treatment options are limited. Endogenous retroviruses (ERVs), specifically human endogenous retrovirus type K (HERV-K), have been proposed to be involved in the propagation of neurodegeneration in ALS. ERVs are genomic remnants of ancient viral infection events, with most being inactive and not retaining the capacity to encode a fully infectious virus. However, some ERVs retain the ability to be activated and transcribed, and ERV transcripts have been found to be elevated within the brain tissue of MND patients. A hallmark of ALS pathology is altered localisation of the transactive response (TAR) DNA binding protein 43 kDa (TDP-43), which is normally found within the nucleus of neuronal and glial cells and is involved in RNA regulation. In ALS, TDP-43 aggregates within the cytoplasm and facilitates neurodegeneration. The involvement of ERVs in ALS pathology is thought to occur through TDP-43 and neuroinflammatory mediators. In this review, the proposed involvement of TDP-43, HERV-K and immune regulators on the onset and progression of ALS will be discussed. Furthermore, the evidence supporting a therapy based on targeting ERVs in ALS will be reviewed. Graphical Abstract

Details

Title: The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy
Authors/Creators: Megan Dubowsky - Flinders University
Frances Theunissen
Jillian M. Carr - Flinders University
Mary-Louise Rogers - Flinders University
Publication Details: Molecular neurobiology, Vol.60(11), pp.6330-6345
Publisher: Springer
Number of pages: 16
Grant note: IG 1950 / Motor Neurone Disease Research Association, Australia, Andrew Butcher 1922 / Motor Neurone Disease Research Australia PhD Scholarship Topup Grant Australian Government Research Training Program Scholarship; Australian Government; Department of Industry, Innovation and Science CAUL
Identifiers: 991005593757307891
Murdoch Affiliation: Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.765 ALS Mechanisms
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior