Immunoreactivity with antibodies against DYRK1A not only in NFTs but also in granules in granulovacuolar degeneration and in corpora amylacea suggests that DYRK1A is involved in all three forms of degeneration and that overexpression of this kinase may contribute to the early onset of these pathologies in DS.
Taken together, these results reveal a potential regulatory link between APP and DYRK1A in DS brains, and suggest that the over-expression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.
These findings strongly suggest a novel mechanism by which the overexpression of Dyrk1A in DS brain causes neurofibrillary degeneration via hyperphosphorylating tau.
There is now compelling evidence that the protein products of two genes on chromosome 21, Down syndrome candidate region 1 (DSCR1) and dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), interact functionally, and that their increased dosage cooperatively leads to dysregulation of the signaling pathways that are controlled by the nuclear factor of activated T cells (NFAT) family of transcription factors, with potential consequences for several organs and systems that are affected in DS individuals.
In human, DYRK1A encodes a serine-threonine kinase but despite its potential involvement in the neurobiological alterations associated with Down syndrome, its physiological function has not yet been defined.
In this review we compile and discuss experimental evidences, which support the involvement of MNB/DYRK1A in several neuropathologies and cognitive deficits of Down syndrome.