c-Jun N-Terminal Kinases in Alzheimer's Disease: A Possible Target for the Modulation of the Earliest Alterations

Given the highly multifactorial origin of Alzheimer's disease (AD) neuropathology, disentangling and orderly knowing mechanisms involved in sporadic onset are arduous. Nevertheless, when the elements involved are dissected into smaller pieces, the task becomes more accessible. This review aimed to describe the link between c-Jun N-terminal Kinases (JNKs), master regulators of many cellular functions, and the early alterations of AD: synaptic loss and dysregulation of neuronal transport. Both processes have a role in the posterior cognitive decline observed in AD. The manuscript focuses on the molecular mechanisms of glutamatergic, GABA, and cholinergic synapses altered by the presence of amyloid-beta aggregates and hyperphosphorylated tau, as well as on several consequences of the disruption of cellular processes linked to neuronal transport that is controlled by the JNK-JIP (c-jun NH2-terminal kinase (JNK)-interacting proteins (JIPs) complex, including the transport of A beta PP or autophagosomes.

Automated summary

This review discusses the involvement of c-Jun N-terminal Kinases (JNKs) in early alterations of Alzheimer's disease (AD), including synaptic loss and dysregulation of neuronal transport. The interactions between JNKs and these processes contribute to cognitive decline in AD, with disruptions in cellular processes such as glutamatergic, GABA, and cholinergic synapses. Furthermore, the review highlights the role of the JNK-JIP complex in controlling neuronal transport and the impact of amyloid-beta aggregates and hyperphosphorylated tau on this process.