Neuronal AMP-activated protein kinase hyper-activation induces synaptic loss by an autophagy-mediated process.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss that leads to the development of cognitive deficits. Synapses are neuronal structures that play a crucial role in memory formation and are known to consume most of the energy used in the brain. Interestingly, AMP-activated protein kinase (AMPK), the main intracellular energy sensor, is hyper-activated in degenerating neurons in several neurodegenerative diseases, including AD. In this context, we asked whether AMPK hyper-activation could influence synapses' integrity and function. AMPK hyper-activation in differentiated primary neurons led to a time-dependent decrease in pre- and post-synaptic markers, which was accompanied by a reduction in synapses number and a loss of neuronal networks functionality.

SUBMITTER: Domise M 

PROVIDER: S-EPMC6399353 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature