Yun SP, Kam TI, Panicker N, Kim S, Oh Y, Park JS, Kwon SH, Park YJ, Karuppagounder SS, Park H, Kim S, Oh N, Kim NA, Lee S, Brahmachari S, Mao X, Lee JH, Kumar M, An D, Kang SU, Lee Y, Lee KC, Na DH, Kim D, Lee SH, Roschke VV, Liddelow SA, Mari Z, Barres BA, Dawson VL, Lee S, Dawson TM, Ko HS. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nat Med. 2018 Jul;24(7):931-938. Epub 2018 Jun 11 PubMed.

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  1. Several preclinical studies have tested the potential neuroprotective effects of glucagon-like peptide-1 (GLP-1) analogs in AD, with promising results. In particular, GLP-1 agonists were shown to reduce levels of oligomeric Aβ and plaques, decrease microglial activation, and improve memory behavior. However, the underlying mechanisms of action remain unclear.

    It has been recently demonstrated that microglial cells can increase GLP-1 and GLP-1 receptor (GLP-1R) expression in response to inflammatory stimuli, and treatment with the GLP-1R agonist EX-4 was able to reduce brain TNF-α levels in an animal model of AD. Inflammation is increasingly recognized as a key contributor to the pathogenesis of neurodegenerative diseases.

    This article describes the protective effects of NLY01, a long-acting GLP-1R agonist, against dopaminergic neuronal loss and behavioral deficits in experimental models of sporadic and familial PD. The relevance of the article lies in the fact that the authors indicate that the mechanism of action is not dependent on neuronal GLP-1R and, for the first time, they suggest a new mechanism involving astrocyte conversion into toxic astrocytes by microglial activation. The paper provides evidence that microglia inhibition mediated by GLP-1 agonist is the primary mechanism of action. These results support that NLY01 and other GLP-1R agonists may have broad protective properties in a variety of neurodegenerative disorders.

    View all comments by Marzia Maria Lecchi

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