Project description:Pathogenic copy number variations (CNVs) contribute to the etiology of neurodevelopmental/neuropsychiatric disorders (NDs). Increased CNV burden has been found to be critically involved in NDs compared with controls in clinical studies. The 1q21.1 CNVs, rare and large chromosomal microduplications and microdeletions, are detected in many patients with NDs. Phenotypes of duplication and deletion appear at the two ends of the spectrum. Microdeletions are predominant in individuals with schizophrenia (SCZ) and microcephaly, whereas microduplications are predominant in individuals with autism spectrum disorder (ASD) and macrocephaly. However, its complexity hinders the discovery of molecular pathways and phenotypic networks. In this review, we summarize the recent genome-wide association studies (GWASs) that have identified candidate genes positively correlated with 1q21.1 CNVs, which are likely to contribute to abnormal phenotypes in carriers. We discuss the clinical data implicated in the 1q21.1 genetic structure that is strongly associated with neurodevelopmental dysfunctions like cognitive impairment and reduced synaptic plasticity. We further present variations reported in the phenotypic severity, genomic penetrance and inheritance.

| S-EPMC8197994 | biostudies-literature

Editorial: Molecular biomarkers in the prediction, diagnosis, and prognosis of neurodegenerative diseases.

Project description: Not available

| S-EPMC10285512 | biostudies-literature

Editorial: Molecular Function and Regulation of Non-coding RNAs in Multifactorial Diseases.

Project description: Not available

| S-EPMC4760206 | biostudies-literature

Immunosenescence: molecular mechanisms and diseases.

Project description:Infection susceptibility, poor vaccination efficacy, age-related disease onset, and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging (known as immunosenescence). During aging, organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers, termed inflammaging. This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases. Thymic involution, naïve/memory cell ratio imbalance, dysregulated metabolism, and epigenetic alterations are striking features of immunosenescence. Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells, and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging. Although the underlying molecular mechanisms remain to be addressed, it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence. Potential counteractive measures will be discussed, including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence. In recent years, immunosenescence has attracted increasing attention for its role in tumor development. As a result of the limited participation of elderly patients, the impact of immunosenescence on cancer immunotherapy is unclear. Despite some surprising results from clinical trials and drugs, it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.

| S-EPMC10182360 | biostudies-literature

Editorial: Diabetic kidney disease: routes to drug development, pharmacology and underlying molecular mechanisms.

Project description: Not available

| S-EPMC10442945 | biostudies-literature

Molecular Mechanisms in Pentanucleotide Repeat Diseases.

Project description:The number of neurodegenerative diseases resulting from repeat expansion has increased extraordinarily in recent years. In several of these pathologies, the repeat can be transcribed in RNA from both DNA strands producing, at least, one toxic RNA repeat that causes neurodegeneration by a complex mechanism. Recently, seven diseases have been found caused by a novel intronic pentanucleotide repeat in distinct genes encoding proteins highly expressed in the cerebellum. These disorders are clinically heterogeneous being characterized by impaired motor function, resulting from ataxia or epilepsy. The role that apparently normal proteins from these mutant genes play in these pathologies is not known. However, recent advances in previously known spinocerebellar ataxias originated by abnormal non-coding pentanucleotide repeats point to a gain of a toxic function by the pathogenic repeat-containing RNA that abnormally forms nuclear foci with RNA-binding proteins. In cells, RNA foci have been shown to be formed by phase separation. Moreover, the field of repeat expansions has lately achieved an extraordinary progress with the discovery that RNA repeats, polyglutamine, and polyalanine proteins are crucial for the formation of nuclear membraneless organelles by phase separation, which is perturbed when they are expanded. This review will cover the amazing advances on repeat diseases.

| S-EPMC8773600 | biostudies-literature

Editorial: Epigenetic Regulation in Cardiovascular Diseases.

Project description: Not available

| S-EPMC8787130 | biostudies-literature