Cdk5: One of the links between senile plaques and neurofibrillary tangles?

Article type: Research Article

Authors: Lee, Ming-Sum | Tsai, Li-Huei^{; *}

Affiliations: Department of Pathology and Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02215, USA

Correspondence: [*] Corresponding author: Li-Huei Tsai, Department of Pathology, Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. Tel.: +1 617 432 1053; Fax: +1 617 432 3975; E-mail: li-huei_tsai@hms.harvard.edu.

Abstract: The relationship between amyloid plaques and neurofibrillary tangles, the two pathologic hallmarks of Alzheimer's disease (AD), is an unknown and controversial subject. However, emerging evidence from genetic and biochemical studies suggests that accumulation of amyloid β peptides may play a causative role in AD pathogenesis. This led to the amyloid hypothesis, which proposes that amyloid β peptides disrupt neuronal metabolic and ionic homeostasis and cause aberrant activation of kinases and/or inhibition of phosphatases. The resulting alteration in kinase and phosphatase activities ultimately leads to hyperphosphorylation of tau and formation of neurofibrillary tangles. Cyclin-dependent kinase 5 (Cdk5) is a tau kinase whose activity is induced by amyloid β peptides. Its deregulation may represent one of the signal transduction pathways that connect amyloid β toxicity to tau hyperphosphorylation. This article reviews the functions and regulation of Cdk5. Evidence that suggests deregulation of Cdk5 activity in AD by virtue of calpain cleavage of its activator p35 to p25 will be discussed.

DOI: 10.3233/JAD-2003-5207

Journal: Journal of Alzheimer's Disease, vol. 5, no. 2, pp. 127-137, 2003