Review of Huntington’s Disease: From Basics to Advances in Diagnosis and Treatment

Abstract

We conducted the present review facing the enormous growth of scientific knowledge in Huntington's disease (HD) and the need for a practical update for general neurologists. HD is a devastating neurodegenerative disease of autosomal dominant inheritance and full penetrance, caused by an expansion of the cytosine-adenine-guanine (CAG) trinucleotide in the huntingtin gene located on chromosome 4. The clinical phenotype varies according to the age of presentation, but it is mainly characterized by cognitive, motor and psychiatric disturbances. Many mechanisms were raised trying to explain the path to neurodegeneration, including disruption of proteostasis, transcription and mitochondrial dysfunction as well as direct toxicity. There has been tremendous progress regarding disease pathogenesis, clinical management and promising new therapeutic avenues including disease-modifying treatments that pose a challenge and a need for a practical approach to be taken by movement disorders specialists and general neurologists.

14-3-3 proteins—a moonlight protein complex with therapeutic potential in neurological disorder: in-depth review with Alzheimer’s disease

“…The relationship between Huntington proteins and 14-3-3 proteins has garnered significant attention in the field of neurobiology. HD is a devastating neurological disorder characterized by the aggregation of mutant HTT and progressive neurodegeneration ( Rojas et al, 2022 ). Studies have revealed that mutant HTT interacts with various cellular proteins, including 14-3-3 proteins ( Shimada et al, 2013 ).…”

Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing

“…These phenotypic markers can be observed in postmortem brain samples from patients or animal models [7]. The disease is accompanied by behavioral symptoms, for instance, impaired motor functions and disturbances of mental and cognitive abilities [8].…”

Focused Ultrasound-Mediated Disruption of the Blood–Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington’s Disease

“…This hereditary neurodegenerative disease is caused by cytosine–adenine–guanine (CAG) trinucleotide repeats in the first exon of the HTT gene that encodes Huntingtin (HTT). This mutation results in the production of mutant HTT (mHTT), which has an expanded polyglutamine (polyQ) domain near the N-terminus of the protein, due to an increase in the number of polyQ-encoding CAG repeats [ 1 , 2 , 3 , 4 ]. MHTT forms aggregates in the cytoplasm and nucleus of neurons and is associated with a cascade of pathogenic processes, including mitochondrial dysfunction, transcriptional dysregulation, altered protein homeostasis and synaptic dysfunction, which ultimately leads to neuronal cell death [ 2 , 5 , 6 , 7 ].…”