Cell cycle re-entry of neurons and reactive neuroblastosis in Huntington's disease: Possibilities for neural-glial transition in the brain

Huntington's disease (HD) is an autosomal dominant pathogenic condition that causes progressive degeneration of GABAergic neurons in the brain. The abnormal expansion of the CAG repeats in the exon 1 of the Huntingtin gene (HTT gene) has been associated with the onset and progression of movement disorders, psychiatric disturbance and cognitive decline in HD. Microglial activation and reactive astrogliosis have been recognized as the key pathogenic cellular events in the brains of HD subjects. Besides, HD has been characterized by induced quiescence of neural stem cells (NSCs), reactive neuroblastosis and reduced survival of newborn neurons in the brain. Strikingly, the expression of the mutant HTT gene has been reported to induce the cell cycle re-entry of neurons in HD brains. However, the underlying basis for the induction of cell cycle in neurons and the fate of dedifferentiating neurons in the pathological brain remain largely unknown. Thus, this review article revisits the reports on the regulation of key signaling pathways responsible for altered cell cycle events in diseased brains, with special reference to HD and postulates the occurrence of reactive neuroblastosis as a consequential cellular event of dedifferentiation of neurons. Meanwhile, a substantial number of studies indicate that many neuropathogenic events are associated with the expression of potential glial cell markers by neuroblasts. Taken together, this article represents a hypothesis that transdifferentiation of neurons into glial cells might be highly possible through the transient generation of reactive neuroblasts in the brain upon certain pathological conditions. [Display omitted] •Post-mitotic neurons re-enter cell cycle and undergo dematuration.•Expression of mutant HTT results in formation of reactive neuroblasts.•The reactive neuroblasts might transit to glial lineage in HD.•Occurrence of neural-glial transition (NGT) is possible in the brain.