Journal of Alzheimer's Disease - Volume 72, issue s1

Authors: Sawant, Neha | Reddy, P. Hemachandra

Article Type: Review Article

Abstract: The purpose of our article is to critically assess the role of phosphorylated tau in Huntington’s disease (HD) progression and pathogenesis. HD is a fatal and pure genetic disease, characterized by chorea, seizures, involuntary movements, dystonia, cognitive decline, intellectual impairment, and emotional disturbances. HD is caused by expanded polyglutamine (polyQ or CAG) repeats within the exon 1 of the HD gene. HD has an autosomal dominant pattern of inheritance with genetic anticipation. Although the HD gene was discovered 26 years ago, there is no complete understanding of how mutant huntingtin (mHTT) selectively targets medium spiny projection neurons in the basal …ganglia of the brain in patients with HD. Several years of intense research revealed that multiple cellular changes are involved in disease process, including transcriptional dysregulation, mitochondrial abnormalities and impaired bioenergetics, defective axonal transport, calcium dyshomeostasis, synaptic damage and caspase, and NMDAR activations. Recent research also revealed that phosphorylated tau and defective GSK-3β signaling are strongly linked to progression of the disease. This article summarizes the recent developments of cellular and pathological changes in disease progression of HD. This article also highlights recent developments in phosphorylated tau and defective GSK-3β signaling and the involvement of calcineurin in HD progression and pathogenesis. Show more

Keywords: Huntington’s disease, hyperphosphorylated tau, medium spiny projection neurons, mitochondrial abnormalities, mutant huntingtin, polyglutamine repeats

DOI: 10.3233/JAD-190851

Citation: Journal of Alzheimer's Disease, vol. 72, no. s1, pp. S177-S191, 2019