MARK4 Inhibited by AChE Inhibitors, Donepezil and Rivastigmine Tartrate: Insights into Alzheimer's Disease Therapy.

ABSTRACT: Microtubule affinity-regulating kinase (MARK4) plays a key role in Alzheimer's disease (AD) development as its overexpression is directly linked to increased tau phosphorylation. MARK4 is a potential drug target of AD and is thus its structural features are employed in the development of new therapeutic molecules. Donepezil (DP) and rivastigmine tartrate (RT) are acetylcholinesterase (AChE) inhibitors and are used to treat symptomatic patients of mild to moderate AD. In keeping with the therapeutic implications of DP and RT in AD, we performed binding studies of these drugs with the MARK4. Both DP and RT bound to MARK4 with a binding constant (K) of 10⁷ M^-1. The temperature dependency of binding parameters revealed MARK-DP complex to be guided by static mode wh

SUBMITTER: Shamsi A 

PROVIDER: S-EPMC7277793 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature