Roles of MAPKs, Including Those Activated by BDNF/TrkB, and Their Contribution in Neurodegenerative Diseases

TL;DR

This paper reviews how BDNF/TrkB signaling and MAPK pathways influence neurons and contribute to neurodegenerative diseases like Alzheimer's and Parkinson's.

Contribution

The paper provides a comprehensive review of how MAPK pathways, especially ERK1/2, p38MAPK, and JNK, influence neuronal survival and death in neurodegenerative diseases.

Findings

BDNF/TrkB signaling activates ERK1/2, which regulates synaptic plasticity in healthy neurons.

Overactivation of ERK1/2 and other MAPKs like p38MAPK and JNK is linked to neurodegeneration.

MAPK pathways contribute to the progression of Alzheimer's, Parkinson's, and Huntington's diseases.

Abstract

Brain-derived growth factor, BDNF, has critical roles in a wide variety of neuronal aspects, including cell survival, differentiation, and synaptic function after their maturation. TrkB, a high-affinity receptor for BDNF, is a major contributor in these neuronal aspects, and its functions are exerted via stimulating intracellular signaling pathways including the mitogen-activated protein kinase (MAPK) pathways. As a family of MAPKs, the functions of ERK1/2, p38MAPK, and JNKs have been extensively studied using in vivo and in vitro neuronal systems. ERK 1/2, a major serine-threonine kinase and belonging to the MAPK family, also works as a downstream molecule after activation of the BDNF/TrkB system. Interestingly, growing evidence has demonstrated that ERK1/2 signaling exerts a positive or negative influence on neurons in both healthy and pathological conditions in the central nervous system (CNS). Indeed, activation of ERK 1/2 stimulated by the BDNF/TrkB system is involved in the regulation of synaptic plasticity. On the other hand, overactivation of ERK1/2 signaling under pathological conditions is closely related to neurodegeneration. Furthermore, cell stress activates p38MAPKs and JNK signaling, contributing to the progression of neurodegeneration. In this review, we show how MAPK pathway signaling affects neuronal fate, including cell survival or cell death, in the CNS. Moreover, we discuss the involvement of overactivation of MAPK signaling in the neurodegeneration observed in Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD).

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