The mammalian family of mitogen-activated protein kinases (MAPKs) includes extracellular
signal-regulated kinase (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK), with each
MAPK signaling pathway consisting of at least three components, a MAPK kinase kinase
(MAP3K), a MAPK kinase (MAP2K), and a MAPK. The MAPK pathways are activated by diverse
extracellular and intracellular stimuli including peptide growth factors, cytokines,
hormones, and various cellular stressors such as oxidative stress and endoplasmic
reticulum stress. These signaling pathways regulate a variety of cellular activities
including proliferation, differentiation, survival, and death. Deviation from the
strict control of MAPK signaling pathways has been implicated in the development of
many human diseases including Alzheimer's disease (AD), Parkinson's disease (PD),
amyotrophic lateral sclerosis (ALS) and various types of cancers. Persistent activation
of the JNK or p38 signaling pathways has been suggested to mediate neuronal apoptosis
in AD, PD, and ALS, whereas the ERK signaling pathway plays a key role in several
steps of tumorigenesis including cancer cell proliferation, migration, and invasion.
In this review, we summarize recent findings on the roles of MAPK signaling pathways
in human disorders, focusing on cancer and neurodegenerative diseases including AD,
PD, and ALS.
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