Mechanistic Insight from Preclinical Models of Parkinson’s Disease Could Help Redirect Clinical Trial Efforts in GDNF Therapy

Autor: Karen M. Delgado-Minjares, Daniel Martinez-Fong, Irma A. Martínez-Dávila, Cecilia Bañuelos, M. E. Gutierrez-Castillo, Víctor Manuel Blanco-Alvarez, Maria-del-Carmen Cardenas-Aguayo, José Luna-Muñoz, Mar Pacheco-Herrero, Luis O. Soto-Rojas
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 21, p 11702 (2021)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms222111702
Popis: Parkinson’s disease (PD) is characterized by four pathognomonic hallmarks: (1) motor and non-motor deficits; (2) neuroinflammation and oxidative stress; (3) pathological aggregates of the α-synuclein (α-syn) protein; (4) neurodegeneration of the nigrostriatal system. Recent evidence sustains that the aggregation of pathological α-syn occurs in the early stages of the disease, becoming the first trigger of neuroinflammation and subsequent neurodegeneration. Thus, a therapeutic line aims at striking back α-synucleinopathy and neuroinflammation to impede neurodegeneration. Another therapeutic line is restoring the compromised dopaminergic system using neurotrophic factors, particularly the glial cell-derived neurotrophic factor (GDNF). Preclinical studies with GDNF have provided encouraging results but often lack evaluation of anti-α-syn and anti-inflammatory effects. In contrast, clinical trials have yielded imprecise results and have reported the emergence of severe side effects. Here, we analyze the discrepancy between preclinical and clinical outcomes, review the mechanisms of the aggregation of pathological α-syn, including neuroinflammation, and evaluate the neurorestorative properties of GDNF, emphasizing its anti-α-syn and anti-inflammatory effects in preclinical and clinical trials.
Databáze: Directory of Open Access Journals
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