Serotonergic Dysfunction in Amyotrophic Lateral Sclerosis and Parkinson's Disease: Similar Mechanisms, Dissimilar Outcomes.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) share similar pathophysiological mechanisms. From a neurochemical point of view, the serotonin (5-hydroxytryptamine; 5-HT) dysfunction in both movement disorders-related to probable lesioning of the raphe nuclei-is profound, and, therefore, may be partially responsible for motor as well as non-motor disturbances. More specifically, in ALS, it has been hypothesized that serotonergic denervation leads to loss of its inhibitory control on glutamate release, resulting into glutamate-induced neurotoxicity in lower and/or upper motor neurons, combined with a detrimental decrease of its facilitatory effects on glutamatergic motor neuron excitation. Both events then may eventually give rise to the well-known clinical motor phenotype.

SUBMITTER: Vermeiren Y 

PROVIDER: S-EPMC5869258 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature