Huntington’s Disease: Complex Pathogenesis and Therapeutic Strategies

Abstract

Huntington’s disease (HD) arises from the abnormal expansion of CAG repeats in the huntingtin gene (HTT), resulting in the production of the mutant huntingtin protein (mHTT) with a polyglutamine stretch in its N-terminus. The pathogenic mechanisms underlying HD are complex and not yet fully elucidated. However, mHTT forms aggregates and accumulates abnormally in neuronal nuclei and processes, leading to disruptions in multiple cellular functions. Although there is currently no effective curative treatment for HD, significant progress has been made in developing various therapeutic strategies to treat HD. In addition to drugs targeting the neuronal toxicity of mHTT, gene therapy approaches that aim to reduce the expression of the mutant HTT gene hold great promise for effective HD therapy. This review provides an overview of current HD treatments, discusses different therapeutic strategies, and aims to facilitate future therapeutic advancements in the field.

Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

“…The immune system plays a major role in the perpetuation and maintenance of the symbiotic relationship between the host and the beneficial commensal bacterial strains. Due to its substantial influence on physiological processes as well as its wide implication in various pathological states, the GM is considered as a new 'metabolic organ,' with major influence not only on the digestive system but also on other organs, notably the CNS [8,[76][77][78][79].…”