Topic: Genetic and Epigenetic Mechanisms in Ageing Related Neurodegenerative Diseases

Aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS), characterized by relentlessly progressive and irreversible neuron loss, may result in motor, cognitive and/or memory impairments. With the rapid increase in the aging population, the related neurodegenerative diseases with scarce effective interventions may create mounting troubles for healthspan and quality of life and lead to a large financial burden. Human genetic factors were regarded as partly underlying the progression of aging-related neurodegenerative diseases. Taking PD for example, approximately 3-5% of PD is driven by a single mutation in known PD-related genes, thus also referred to as monogenic or familial PD. Mutations in the synuclein alpha gene (SNCA), the leucine-rich repeat kinase 2 gene (LRRK2), the parkin RBR E3 ubiquitin-protein ligase gene (PRKN), the PTEN induced kinase 1 gene (PINK1), and the glucosylceramidase beta gene (GBA) are the most common genetic factors clearly linked to PD. The largest meta-analysis of genome-wide association studies also found that genetic variants at 90 loci collectively contribute to 16-36% of the heritable risk for non-monogenic PD. With the explosive development of high-throughput technologies, more genes and gene variants will be uncovered to present improved pathophysiological clues. In addition, converging evidence implicates that the dysregulation of epigenetic mechanisms plays a role in pathologies of aging-related neurodegenerative diseases. Epigenetic alterations, such as methylation of DNA, aberrant modifications of histone, and deregulated expression/activity of MicroRNAs (miRNAs), strongly influence gene expression and cellular differentiation, then the development and/or progression of several aging-related neurodegenerative diseases. Recently, owing to a more thorough understanding of the neural network, the most interest has been focused on epigenetics, and further epigenetic researches on both healthy and diseased human brain are required.

In this Special Issue, we welcome all types of papers exploring the genetic and epigenetic risk factors and the pathogenic mechanisms involved in aging-related neurodegenerative diseases. The relevant topics include but are not limited to relevant gene variants, copy number variations (CNVs), epigenetic modifications, and cellular and animal studies revealing the biological basis of aging-related neurodegenerative diseases. The potential hallmarks and therapeutic targets based on pathogenesis can also be discussed to provide investigators with foundations to develop promising prevention and treatment strategies.

30 Apr 2023