Transition metal nickel prevents Tau aggregation in Alzheimer's disease

Abstract

Alzheimer's disease is the leading cause of dementia, effecting majority of aged people worldwide. The multifaceted effectors of Alzheimer's disease primarily include Tau, amyloid-β along with hyper activation of kinases, oxidative stress and mutations etc., makes it challenging to design therapeutics. Tau is a microtubule-associating protein, which is subjected to cellular stress resulting in the formation of neurofibrillary tangles, leading to loss of affinity for microtubules. This causes loss of microtubule stability and in turn alters axonal integrity. In the present work, emphasis towards understanding interaction of nickel with Tau was made. Metals such as iron, zinc, copper and lead etc., are known to modulate Tau conformation and enhance its aggregation. Our results showed the deliverance of Tau aggregation by nickel and its synthetic morpholine conjugate. Nickel prevents aggregation by inducing degradation of Tau as evidenced by SDS-PAGE and TEM. Nickel and the synthetic conjugate being non-toxic to neuro2a cells and prevent Tau aggregation, might direct these complexes to overcome AD.