DSCR1(Adapt78)‐‐A Janus Gene Providing Stress Protection but Causing Alzheimer's Disease?

Abstract

Alzheimer's disease is associated with the formation of paired helical filaments composed of hyperphospharylated tau protein. Phosphatase 2B, calcineurin can dephosphorylate the tau protein and, therefore, might prevent the assembly of paired helical filaments and even Alzheimer's disease. Calcipressin 1, the DSCR1(Adapt78) gene product, can bind and inactivate calcineurin. Here we hypothesize that while short‐term induction of calcipressin1 can provide stress protection, its long‐term or chronic induction may cause gradual accumulation of hyperphosphorylated tau protein, eventually leading to Alzheimer's disease. IUBMB Life, 55: 29‐31, 2003

Chronic Expression of RCAN1-1L Protein Induces Mitochondrial Autophagy and Metabolic Shift from Oxidative Phosphorylation to Glycolysis in Neuronal Cells

“…For example, it has been recently recognized that mitochondrial dysfunction is an important factor in induction of Alzheimer disease (40,41). We have previously proposed that overexpression of RCAN1s may lead to Alzheimer disease by inducing Tau hyperphosphorylation (7,8,15,42). Now our results suggest that it may also contribute to this disease by diminishing mitochondrial functions.…”

“…Chronic RCAN1 induction, however, is associated with Down syndrome and Alzheimer disease (2, 7), which suggests that the gene can also be harmful. To reconcile these findings, it was hypothesized that RCAN1 may exert protective effects if induced for only a short time but harmful effects if induced chronically (8). However, the mechanisms by which RCAN1s may protect or harm are incompletely understood.…”

Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensin II-exposed cardiomyocytes

“…These results support the hypothesis that overexpressed Rcan1-1L protects human cardiomyocytes from Ang II-activated oxidative stress through induction of mitochondrial autophagy. A previous study demonstrated that RCAN1 protein, through transient induction for 2-6 h, can protect against acute stress [37,38]. However, chronic RCAN1 overexpression is implicated in Down syndrome and Alzheimer disease [39][40][41].…”

Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease

“…RCAN1 inhibits calcineurin, a p-Tau phosphatase, leading to Tau hyperphosphorylation [38]. In fact, elevated levels of RCAN1 protein are associated with AD [10,[39][40][41] and are also associated with mitochondrial metabolism impairment and mitophagy [42].…”