Mechanistic Insight from Preclinical Models of Parkinson’s Disease Could Help Redirect Clinical Trial Efforts in GDNF Therapy
| Autor: | Maria E. Gutierrez-Castillo, Mar Pacheco-Herrero, Daniel Martinez-Fong, Karen M Delgado-Minjares, José Luna-Muñoz, Cecilia Bañuelos, Irma A Martínez-Dávila, Luis O Soto-Rojas, Victor Manuel Blanco-Alvarez, Maria-Del-Carmen Cardenas-Aguayo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Parkinson's disease
neurotrophic factors QH301-705.5 animal diseases Drug Evaluation Preclinical Disease Review Protein Aggregation Pathological Catalysis neuroinflammation Inorganic Chemistry α-synuclein Neurotrophic factors Glial cell line-derived neurotrophic factor Medicine Animals Humans neurodegenerative diseases anti-inflammatory therapy Glial Cell Line-Derived Neurotrophic Factor Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Neuroinflammation Clinical Trials as Topic biology business.industry Organic Chemistry Neurodegeneration Dopaminergic Parkinson Disease General Medicine medicine.disease Computer Science Applications Clinical trial Disease Models Animal Chemistry nervous system Neuroinflammatory Diseases biology.protein alpha-Synuclein anti-α-synuclein therapy business Neuroscience neurorestoration |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 11702, p 11702 (2021) |
| ISSN: | 1422-0067 |
| 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: | OpenAIRE |
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