Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics

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dc.contributor.authorPĂ©rez, Rodrigo
dc.contributor.authorCisternas, Marisol
dc.contributor.authorSepĂșlveda, Denisse
dc.contributor.authorTroncoso, Paulina
dc.contributor.authorVidal, Rene
dc.date.accessioned2023-01-24T16:33:58Z
dc.date.available2023-01-24T16:33:58Z
dc.date.issued2023
dc.description.abstractNeurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.
dc.description.versionVersiĂłn publicada
dc.identifier.citationPĂ©rez-Arancibia R, Cisternas-Olmedo M, SepĂșlveda D, Troncoso-Escudero P and Vidal RL (2023) Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics. Front. Neurosci. 16:1084493. doi:10.3389/fnins.2022.1084493
dc.identifier.doihttps://doi.org/10.3389/fnins.2022.1084493
dc.identifier.urihttps://repositorio.udd.cl/handle/11447/6990
dc.language.isoen
dc.subjectParkinson's disease
dc.subjectHuntington's disease
dc.subjectDrug repurposing
dc.subjectPharmacological therapy
dc.subjectSmall molecules
dc.subjectNatural products
dc.titleSmall molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics
dc.typeArticle
dcterms.accessRightsAcceso abierto
dcterms.sourceFrontiers in Neuroscience

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