Molecular spectrum, family screening and genetic counselling of Spinocerebellar Ataxia (SCA) cases in an Indian scenario

Vishwakarma, Priyanka; Agarwal, Sarita; Dean, Deepika Delsa; Muthuswamy, Srinivasan; Mandal, Kausik

doi:10.1080/01677063.2021.1940172

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…These CAG repeats can be found in untranslated regions (UTRs) or the protein-coding area of related genes [2]. Disorders result from protein mutations in the majority of SCAs including 1, 2, 3, 6, 7, 12, and 17 [3,4]. In fact, during translation, CAG codes for glutamine (Q); but, because of mutations, enlarged CAG repeats translate into polyglutamine (polyQ) tracts.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, during translation, CAG codes for glutamine (Q); but, because of mutations, enlarged CAG repeats translate into polyglutamine (polyQ) tracts. These kinds of illnesses are classified as polyglutamine (polyQ) diseases because these polyQ tracts are integrated into mutant proteins [4]. These mutant proteins cause a variety of pathological conditions, such as gain‐of‐toxic function, accumulation of normal protein function to a toxic level, aggregate formation, and sequestration of other proteins like polyglutamine tract‐binding domain protein (PQBP‐1) and CREB‐binding protein (CBP) [1].…”

Section: Introductionmentioning

confidence: 99%

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In Silico Prediction of Potential Inhibitors for Targeting RNA CAG Repeats via Molecular Docking and Dynamics Simulation: A Drug Discovery Approach

Singh,

Joshi

et al. 2024

J of Cellular Biochemistry

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Spinocerebellar ataxia (SCA) is a rare neurological illness inherited dominantly that causes severe impairment and premature mortality. While each rare disease may affect individuals infrequently, collectively they pose a significant healthcare challenge. It is mainly carried out due to the expansion of RNA triplet (CAG) repeats, although missense or point mutations can also be induced. Unfortunately, there is no cure; only symptomatic treatments are available. To date, SCA has about 48 subtypes, the most common of these being SCA 1, 2, 3, 6, 7, 12, and 17 having CAG repeats. Using molecular docking and molecular dynamics (MD) simulation, this study seeks to investigate effective natural herbal neuroprotective compounds against CAG repeats, which are therapeutically significant in treating SCA. Initially, virtual screening followed by molecular docking was used to estimate the binding affinity of neuroprotective natural compounds toward CAG repeats. The compound with the highest binding affinity, somniferine, was then chosen for MD simulation. The structural stability, interaction mechanism, and conformational dynamics of CAG repeats and somniferine were investigated via MD simulation. The MD study revealed that during the simulation period, the interaction between CAG repeats and somniferine stabilizes and results in fewer conformational variations. This in silico study suggests that Somniferine can be used as a therapeutic medication against RNA CAG repeats in SCA.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Silico Prediction of Potential Inhibitors for Targeting RNA CAG Repeats via Molecular Docking and Dynamics Simulation: A Drug Discovery Approach

Singh,

Joshi

et al. 2024

J of Cellular Biochemistry

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A General Neurologist's Practical Diagnostic Algorithm for Atypical Parkinsonian Disorders

Bruno,

Dhall,

Duquette

et al. 2024

Neur Clin Pract

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Purpose of ReviewThe most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require excluding competing diagnoses without clearly specifying how to do that. Validated diagnostic criteria are not available at all for many of the other common APDs, including normal pressure hydrocephalus (NPH), vascular parkinsonism (VP), or drug-induced parkinsonism (DIP). APDs also include conditions of structural, genetic, vascular, toxic/metabolic, infectious, and autoimmune origin. Their differential diagnosis can be challenging early in the course, if the presentation is atypical, or if a rare or non-neurodegenerative condition is present. This review equips community general neurologists to make an early provisional diagnosis before, or in place of, referral to a tertiary center. Early diagnosis would allay diagnostic uncertainty, allow prompt symptomatic management, provide disease-specific information and support resources, avoid further pointless testing and treatments, and create the possibility of trial referral. Recent FindingsWe address 64 APDs using one over-arching flow diagram and a series of detailed tables. Most instances of APDs can be diagnosed with a careful history and neurological exam, along with a noncontrast brain MRI. Additional diagnostic tests are rarely needed but are delineated where applicable. Our diagnostic algorithm encourages referral to a tertiary center whenever the general neurologist feels it would be in the patient's best interest. Our algorithm emphasizes that the diagnosis of APDs is an iterative process, refined with the appearance of new diagnostic features, availability of new technology, and advances in scientific understanding of the disorders. Clinicians' proposals for all diagnostic tests for the APDs, including repeat visits, should be discussed with patients and their families to ensure that the potential information to be gained aligns with their larger clinical goals.

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Molecular spectrum, family screening and genetic counselling of Spinocerebellar Ataxia (SCA) cases in an Indian scenario

Cited by 2 publications

References 37 publications

In Silico Prediction of Potential Inhibitors for Targeting RNA CAG Repeats via Molecular Docking and Dynamics Simulation: A Drug Discovery Approach

In Silico Prediction of Potential Inhibitors for Targeting RNA CAG Repeats via Molecular Docking and Dynamics Simulation: A Drug Discovery Approach

A General Neurologist's Practical Diagnostic Algorithm for Atypical Parkinsonian Disorders

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