Background: Genome-wide association studies (GWAS) have been used to explore the connections between genotypes and phenotypes by comparing the genotype frequencies of genetic changes in individuals with similar origins but distinct traits. Objectives: The aim is to employ the GWAS catalog to identify and investigate the various correlations between genotypes and phenotypes of the REST gene. Method: In this study, we utilized a large dataset of GWAS comprising 62,218,976 individuals in 112 studies and 122 associations with 122 traits (www.ebi.ac.uk/gwas/genes/REST) from European, Asian, Hispanic, African ancestry up to 28 February 2023. Protein-association network evaluation and gene ontology enrichment study was utilized to evaluate the biological function of the discovered gene modules. Results: We identified several associations for both neurodevelopmental and neurodegenerative disorders linked to REST, as well as its mapped gene modules and their functional relationship networks. Conclusion: This work offers fresh insights into identifying risk loci of neurological disorders caused by REST.

Objective The aim of this study was to investigate the clinical efficacy of exercise intervention in the treatment of patients with Alzheimer's disease (AD) by meta‐analysis. Methods From January 2000 to January 2022, PubMed, Web of Science, Embase, CNKI, and WanFang databases were searched for all studies on the clinical efficacy of exercise intervention in the treatment of AD patients. Stata 17.0 statistical software was used for meta‐analysis. Results Specifically, data of 983 patients were subjected to meta‐analysis, including 463 patients in the control group (conventional drug therapy) and 520 patients in the treatment group (physical exercise on the basis of conventional therapy). The results of meta‐analysis showed that Mini‐Mental State Examination (MMSE) score and Activities of Daily Living Scale (ADL) score in the treatment group were significantly higher than those in the control group. Further subgroup analysis of exercise intervention >16 weeks found that MMSE and ADL scores in the treatment group were significantly higher than those in the control group. Subgroup analysis of exercise intervention ≤16 weeks demonstrated that MMSE and ADL in the treatment group were higher than those in the control group. In addition, the treatment group had a significant lower Neuropsychiatric Inventory (NPI) score compared with the control group (SMD = –0.76, 95% CI (–1.37, –0.16), p = .013); subgroup analysis showed that the NPI score in the treatment group were lower than that in the control group when exercise intervention was >16 weeks [SMD = –1.01, 95% CI (–1.99, –0.04), p = .042] and ≤16 weeks [SMD = 0.43, 95% CI (–0.82, –0.03), p = .034]. Conclusion Exercise intervention can improve the neuropsychiatric symptoms, activities of daily living and cognitive function of AD patients, but the improvement is not significant in case of exercise intervention ≤16 weeks.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD), is an autosomal dominant neurodegenerative disorder that predominantly involves the cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. SCA3 presents strong phenotypic heterogeneity and its causative mutation of SCA3 consists of an expansion of a CAG tract in exon 10 of the ATXN3 gene, situated at 14q32.1. The ATXN3 gene is ubiquitously expressed in neuronal and non-neuronal tissues, and also participates in cellular protein quality control pathways. Mutated ATXN3 alleles present about 45 to 87CAG repeats, which result in an expanded polyglutamine tract in ataxin-3. After mutation, the polyQ tract reaches the pathological threshold (about 50 glutamine residues); the protein is considered that it might gain a neurotoxic function through some unclear mechanisms. We reviewed the literature on the pathogenesis and therapeutic strategies of spinocerebellar ataxia type 3 patients. Conversion of the expanded protein is possible by enhancing protein refolding and degradation or preventing proteolytic cleavage and prevents the protein to reach the site of toxicity by altering its ability to translocate between the nucleus and cytoplasm. Proteasomal degradation and enhancing autophagic aggregate clearance are currently proposed remarkable therapy. In spite of extensive research, the molecular mechanisms of cellular toxicity resulting from mutant ataxin-3 remain no preventive treatment is currently available. These therapeutic strategies might be able to improve sign symptoms of SCA3 as well as slow the disease progression.