DOI: 10.1002/alz.072751 ISSN: 1552-5260

Circulatory GSK‐3beta a new target against Alzheimer’s disease

Sharmistha Dey, Shiwani Kumari, Abhinay Kumar Singh, Yudhishthir Yadav
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology

Abstract

Background

Alzheimer’s disease (AD) is the progressive brain disorder which degenerate brain cells connection and causes memory loss. Though, AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage and early diagnosis requires clear understanding of pathogenesis at molecular level. Overactivity of GSK‐3β and p53 accounts for tau hyperphosphorylation, and amyloid‐β plaque

Method

We explored GSK‐3β and p53 as blood‐based biomarkers for early detection of AD. Methods: The levels of GSK‐3β, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using Western blot in serum from AD, mild cognitive impairment (MCI), and geriatric‐control (GC) subjects. The neurotoxic SH‐SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect.

Result

GSK‐3β, p53, and their phosphorylated state were significantly over expressed (p>0.001) in AD, MCI compared to GC and can differentiate AD, MCI from GC. The expression level of GSK‐3β and p53 proteins were found to be downregulated in a dose‐dependent manner after the treatment with EO in amyloid‐β induced neurotoxic cells.

Conclusion

These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

More from our Archive