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Cuello-Almarales, D.

Publications and source records attributed to Cuello-Almarales, D..

2 recordsLinked to original sources

Blood glucose homeostasis in patients with mild to moderate Spinocerebellar Ataxia type 2

BackgroundSpinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder that shows cerebellar glucose hypometabolism, systemic hypermetabolism and weight loss. This study aimed to explore novel molecular biomarker candidates for SCA2, based on the assessment of blood glucose homeostasis. MethodsA case-control and correlational study was conducted in 79 Cuban patients with SCA2 and 83 sex- and age-matched control subjects during a fasting state. A subset of 20 SCA2 patients and 19 control individuals underwent an oral glucose tolerance test (OGTT). Several indices for assessing blood glucose homeostasis, derived from the fasting state or the OGTT, were included in the study. ResultsFasting glucose levels showed a small increase, whereas the QUICKI index for insulin sensitivity was slightly decreased among patients. Markers of glucose homeostasis derived from the OGTT were no different between patients and controls. Fasting insulin levels, QUICKI, McAuleys, HOMA2-%S, HOMA2-IR, and HOMA2-%{beta} indices showed weak to moderate correlations with markers of body composition. McAuleys, TyG, HOMA2-IR, and HOMA2-%{beta} indices correlated with the age at onset, progression rate, or INAS count. ConclusionsSCA2 patients with mild to moderate ataxia do not have any major alteration in blood glucose homeostasis. Markers of glucose homeostasis associate with body composition and has modifying effects on disease severity and progression rate in patients with SCA2, with McAuleys index showing effects more consistently. Further studies are needed to describe the changes in blood glucose homeostasis in the different stages of disease, and to confirm the validity of McAuleys index as a candidate biomarker for SCA2 clinical severity and progression.

physiology↗

Multiomics approach identifies SERPINB1 as candidate progression biomarker for Spinocerebellar Ataxia type 2

BackgroundSpinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder, and variants in its disease protein Ataxin-2 act as modifiers in the progression of Amyotrophic Lateral Sclerosis. There are no reliable molecular progression biomarkers for SCA2. ObjectivesThe aim of this study was to define novel molecular progression biomarker candidates for SCA2. MethodsUsing cerebellar and cervicothoracic spinal cord RNA from Atxn2-CAG100-KnockIn and wildtype mice, a multi-omics study was conducted, followed by validation in mice and humans. Global transcriptome studies were conducted using the Clariom D microarray. Extracted proteins were analyzed by LC-MS/MS for global proteomics, and Immobilized Metal Affinity Chromatography for phosphoproteomics. Validation assessed expression by RT-qPCR, and protein abundance by quantitative immunoblots and ELISA. Patients with SCA2 were diagnosed following standard procedures, and the age at onset, SARA score, INAS count, and disease duration were used as clinical severity markers. ResultsVenn diagram comparisons across all OMICS datasets indicated that only Serpinb1a-transcript, SERPINB1A-protein and -phosphopeptides were consistently downregulated at terminal stage in 14-month-old KnockIn mice. Expression studies in cerebellum and spinal cord from 10 weeks (pre-manifest), 6-month-old (early ataxic), and 14-month-old (late ataxic stage) mice confirmed this progressive decrease at mRNA and protein level. SERPINB1 plasma levels were significantly lower in SCA2 patients, and displayed a significant association with the CAG repeat length at expanded ATXN2 alleles and the age at onset, also showing a trend towards significance with the SARA score. ConclusionsSERPINB1 was identified as novel promising biomarker with specificity for SCA2 pathomechanisms.

molecular biology↗