Ataxin-2 gene: a powerful modulator of neurological disorders.
TLDR
The role of ATXN2 and its variants in association with SCA2 and several other neurological diseases has been discussed in this paper, including motor neuron disease, spinocerebellar ataxia 3 (SCA3), and familial amyloidosis polyneuropathy.Abstract:
Purpose of review To provide an update on the role of Ataxin-2 gene (ATXN2) in health and neurological diseases. Recent findings There is a growing complexity emerging on the role of ATXN2 and its variants in association with SCA2 and several other neurological diseases. Polymorphisms and intermediate cytosine adenine guanine alleles in ATXN2 establish this gene as a powerful modulator of neurological diseases including lethal neurodegenerative conditions such as motor neuron disease, spinocerebellar ataxia 3 (SCA3), and peripheral nerve disease such as familial amyloidosis polyneuropathy. This role is in fact far wider than the previously described for polymorphism in the prion protein (PRNP) gene. Positive data from antisense oligo therapy in a murine model of SCA2 suggest that similar approaches may be feasible in humans SCA2 patients. Summary ATXN2 is one of the few genes where a single gene causes several diseases and/or modifies several and disparate neurological disorders. Hence, understanding mutagenesis, genetic variants, and biological functions will help managing SCA2, and several human diseases connected with dysfunctional pathways in the brain, innate immunity, autophagy, cellular, lipid, and RNA metabolism.read more
Citations
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Insights from analyses of low complexity regions with canonical methods for protein sequence comparison
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Antisense oligonucleotides targeting basal forebrain ATXN2 enhances spatial memory and ameliorates sleep deprivation‐induced fear memory impairment in mice
Tao Ma,Longqiang Feng,Shinan Wei,Ying-Ying Wang,Guanhua Li,Yan Lu,Yingxin Zhang,Yang Chu,Wei Wang,Hao Zhang +9 more
TL;DR: In this article , Antisense oligonucleotides (ASOs) targeting ATXN2 were used as a potential therapy for spinocerebellar ataxia, whose pathogenic mechanism associates with reduced BDNF expression.
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Are ATXN2 variants modifying our understanding about neural pathogenesis, phenotypes, and diagnostic?
TL;DR: The ATXN2 gene encodes a cytosolic protein (ataxin-2) with pleiotropic functions (see below) which contains a number of exonic Cytosine-Adenine-Guanine (CAG)repeats which encode a polyglutamine tract (polyQ) in the N-terminal intrinsically disordered region (IDR) of the protein.
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TR-FRET-Based Immunoassay to Measure Ataxin-2 as a Target Engagement Marker in Spinocerebellar Ataxia Type 2
Jessica Bux,Nesli-Ece Sen,Isa-Maria Klink,Stefan Hauser,Matthis Synofzik,Ludger Schöls,Georg Auburger,Olaf Riess,Jeannette Hübener-Schmid +8 more
TL;DR: In this paper , the amount of soluble polyQ-expanded ataxin-2 in human biofluids was measured using time-resolved fluorescence energy transfer (TR-FRET) and validated measurements in human cell lines including iPSC-derived cortical neurons.
References
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Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis
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TL;DR: Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia, which could help to define biomarkers that can stage presymPTomatic disease and track disease progression.