The emerging molecular mechanisms for mitochondrial dysfunctions in FXTAS

Dhruv Gohel, Nicolas Charlet Berguerand, Flora Tassone, Rajesh Singh

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by an expansion of 55-200 CGG repeats at 5UTR of FMR1 gene, known as premutation. The main clinical and neuropathological features of FXTAS include progressive intention tremor, gait ataxia, neuronal cell loss and presence of ubiquitin-positive intranuclear inclusions in neurons and astrocytes. Various mitochondrial dysfunctions are reported in in vitro/vivo models of FXTAS; however, the molecular mechanisms underlying such mitochondrial dysfunctions are unclear. CGG expansions are pathogenic through distinct mechanisms involving RNA gain of function, impaired DNA damage repair and FMRpolyG toxicity. Here, we have systematically reviewed the reports of mitochondrial dysfunctions under premutation condition. We have also focused on potential emerging mechanisms to understand mitochondrial associated pathology in FXTAS. This review highlights the important role of mitochondria in FXTAS and other related disorders; and suggests focus of future studies on mitochondrial dysfunction along with other prevailing mechanisms to alleviate neurodegeneration.

Original languageEnglish (US)
Article number165918
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number12
DOIs
StatePublished - Dec 1 2020

Keywords

  • FMRpolyG
  • FXTAS
  • Inflammation
  • miRNAs
  • Mitochondrial dysfunctions
  • RNA gain of function

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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