Ataxin-2 gene: a powerful modulator of neurological disorders

Laffita-Mesa, José Miguel; Paucar, Martin; Svenningsson, Per

doi:10.1097/wco.0000000000000959

Cited by 20 publications

(20 citation statements)

References 72 publications

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“…However, current knowledge says that homopolymer length may affect protein function. For instance, poly-Q region may cause neurological disease if it reach a given length [ 75 ]. Therefore, differences in lengths should be somehow penalized in LCR alignments for example by comparing them globally.…”

Section: Discussionmentioning

confidence: 99%

Insights from analyses of low complexity regions with canonical methods for protein sequence comparison

Jarnot

Ziemska-Legięcka

Grynberg

et al. 2022

Briefings in Bioinformatics

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Low complexity regions are fragments of protein sequences composed of only a few types of amino acids. These regions frequently occur in proteins and can play an important role in their functions. However, scientists are mainly focused on regions characterized by high diversity of amino acid composition. Similarity between regions of protein sequences frequently reflect functional similarity between them. In this article, we discuss strengths and weaknesses of the similarity analysis of low complexity regions using BLAST, HHblits and CD-HIT. These methods are considered to be the gold standard in protein similarity analysis and were designed for comparison of high complexity regions. However, we lack specialized methods that could be used to compare the similarity of low complexity regions. Therefore, we investigated the existing methods in order to understand how they can be applied to compare such regions. Our results are supported by exploratory study, discussion of amino acid composition and biological roles of selected examples. We show that existing methods need improvements to efficiently search for similar low complexity regions. We suggest features that have to be re-designed specifically for comparing low complexity regions: scoring matrix, multiple sequence alignment, e-value, local alignment and clustering based on a set of representative sequences. Results of this analysis can either be used to improve existing methods or to create new methods for the similarity analysis of low complexity regions.

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Section: Discussionmentioning

confidence: 99%

Insights from analyses of low complexity regions with canonical methods for protein sequence comparison

Jarnot

Ziemska-Legięcka

Grynberg

et al. 2022

Briefings in Bioinformatics

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“…ATXN2 is a ubiquitous RNA-binding protein with a polyglutamine (polyQ ) CAG repeat in its coding region. ATXN2 has roles in regulating many cellular processes, including stress granule formation, starvation and stress response, translation, RNA processing, metabolism, mitochondrial function, and calcium signaling [85,86]. Expansions of polyglutamine repeat of ATXN2 have been implicated in spinocerebellar ataxia 2 (SCA2) and amyotrophic lateral sclerosis (ALS) [83].…”

Section: Atxn2mentioning

confidence: 99%

“…Expansions of polyglutamine repeat of ATXN2 have been implicated in spinocerebellar ataxia 2 (SCA2) and amyotrophic lateral sclerosis (ALS) [83]. In addition to causing SCA2 and increasing the risk of developing ALS, mutations in ATXN2 may play a role in a handful of other diseases, including Parkinson's disease (PD), spinocerebellar ataxia type I (SCA1), Machado-Joseph Disease (SCA3), tauopathies, POAG, obesity and type I diabetes [85,86].…”

Section: Atxn2mentioning

confidence: 99%

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The Molecular Mechanisms of Trabecular Meshwork Damage in POAG and Treatment Advances

Tang¹,

Tang²,

Wang³

et al. 2023

Glaucoma - Recent Advances and New Perspectives

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Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness affecting over 60 million people worldwide. Elevated intraocular pressure (IOP) due to dysfunction of trabecular meshwork (TM) is the most significant and the only known modifiable risk factor for POAG. Although, glaucomatous TM damage is known to be mainly responsible for IOP elevation, none of the current treatments target TM pathology. This is partly due to an incomplete understanding of the pathophysiological mechanisms of TM damage. In this review, we summarized pathological changes of TM damage in POAG and our current knowledge of the mechanisms of glaucomatous TM damage, particularly focusing on linking the genetic factors of POAG (e.g., mutations and variants in POAG risk genes, risk loci, dysregulation of gene expression) to molecular pathways of pathogenesis in TM. In terms of treatment, reduction of IOP is the mainstream strategy that can be achieved by medical, laser or surgical treatment. IOP lowering drugs, laser or surgery can lower IOP, but do not reverse or restore the oxidative stress or other TM damage in POAG. Additionally, antioxidants, ginkgo biloba extract and nutrients could be a promising treatment for POAG.

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“…Age-and sex-dependent association of the CHRNA3/5 locus with longevity has been validated in a meta-analysis [76] . The effect on the life span might be secondary to disease-susceptibility because of the association of the variants at this locus with smoking, nicotine dependence, lung cancer, and peripheral arterial disease [91] .…”

Section: Clesr2/sort1/psrc1 Locusmentioning

confidence: 99%

Genetic basis of cardiovascular aging is at the core of human longevity

Marian

2022

J Cardiovasc Aging

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Aging is an archetypical complex process influenced by genetic and environmental factors. Genetic variants impart a gradient of effect sizes, albeit the effect sizes seem to be skewed toward those with small effect sizes. On one end of the spectrum are the rare monogenic premature aging syndromes, such as Hutchinson Gilford Progeria Syndrome, whereby single nucleotide changes lead to rapidly progressive premature aging. On the end of the spectrum is the complex, slowly progressive process of living to an arbitrary-defined old age, i.e., longevity. Whereas the genetic basis of rare premature aging syndromes has been elucidated, only a small fraction of the genetic determinants of longevity and life span, time from birth to death, have been identified. The latter point to the complexity of the process and involvement of myriad of genetic and non-genetic factors and hence, the diluted effect of each determinant on longevity. The genetic discoveries point to the involvement of the DNA damage and activation of the DNA damage response pathway, particularly in the premature aging syndromes. Likewise, the insulin/insulin-like growth factor 1/mTOR/FOXO pathways have emerged as major regulators of life span. A notable fraction of the genetic variants that are associated with life span is also associated with age-related cardiovascular diseases, such as coronary artery disease and dyslipidemia, which places cardiovascular aging at the core of human life span. The clinical impact of the discoveries pertains to the identification of the pathways that are involved in life span, which might serve as targets of interventions to prevent, slow, and even possibly reverse aging.

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Ataxin-2 gene: a powerful modulator of neurological disorders

Cited by 20 publications

References 72 publications

Insights from analyses of low complexity regions with canonical methods for protein sequence comparison

Insights from analyses of low complexity regions with canonical methods for protein sequence comparison

The Molecular Mechanisms of Trabecular Meshwork Damage in POAG and Treatment Advances

Genetic basis of cardiovascular aging is at the core of human longevity

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