SARS-CoV-2 dysregulation of PTBP1 and YWHAE/Z gene expression: A primer of neurodegeneration

Abstract

SARS-CoV-2 neurotropism has been increasingly recognized by its imaging and syndromic manifestations in the literature. The purpose of this report is to explore the limited yet salient current evidence that SARS-CoV-2's host genomic targets PTBP1 and the 14-3-3 protein isoform encoding genes YWHAE and YWHAZ may be hold the key to understanding how neurotropism triggers neurodegeneration and how it may contribute to the onset of neurodegenerative disease. Considering that PTBP1 silencing in particular has recently been shown to reverse clinical parkinsonism and induce neurogenesis, as well as the known interactions of PTBP1 and YWHAE/Z with coronaviruses - most notably 14-3-3 and SARS-CoV, recent studies reinvigorate the infectious etiology hypotheses on major neurodegenerative disease such as AD and iPD. Considering that human coronaviruses with definite neurotropism have been shown to achieve long-term latency within the mammalian CNS as a result of specific accommodating mutations, the corroboration of genomic-level evidence with neuroimaging has vast potential implications for neurodegenerative disease.

Keywords: 14-3-3 proteins; Epigenetics; Neurodegeneration; Neurotropism; PTBP1; SARS-CoV-2.