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Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Patients Stratification Strategies to Optimize the Effectiveness of Scavenging Biogenic Aldehydes: Towards a Neuroprotective Approach for Parkinson's Disease

Author(s): Anna Masato , Michele Sandre, Angelo Antonini and Luigi Bubacco*

Volume 19, Issue 10, 2021

Published on: 03 February, 2021

Page: [1618 - 1639] Pages: 22

DOI: 10.2174/1570159X19666210203162617

Price: $65


Parkinson’s disease (PD) is a clinically heterogeneous disorder with a multi-factorial pathology. Various molecular mechanisms are involved in the pathogenesis of PD, converging to oxidative stress and proteinopathy. The accumulation of reactive aldehydes (i.e., the dopamine metabolite DOPAL, lipid-peroxidation products, and advanced glycation end-products) has been reported in PD patients’ brains. Aldehydes easily react with primary amines such as lysine residues, which are involved in several regulatory processes in cells. Therefore, aldehyde adducts lead to severe consequences, including neuronal proteostasis, mitochondrial dysfunction, and cell death. In this review, we analyzed the scavenging role of amines toward toxic aldehydes in the brain. Interestingly, small molecules like metformin, rasagiline, hydralazine are already clinically available and used in the therapy for PD and other diseases. Hence, we propose to reevaluate this class of drugs as a disease-modifiers for PD, and we suggest that improved analysis of their pharmacology and bioavailability in the brain, together with a more precise patients stratification, should be considered before planning future clinical trials.

Keywords: Parkinson's disease, aldehyde, scavenger, neuroprotection, patients stratification, biomarkers.

Graphical Abstract

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