Parkinson's Disease (PD) is characterized both by the loss of dopaminergic neurons in the substantia nigra and the presence of cytoplasmic inclusions called Lewy Bodies. These Lewy Bodies contain the aggregated α-synuclein (α-syn) protein, which has been shown to be able to propagate from cell to cell and throughout different regions in the brain. Due to its central role in the pathology and the lack of a curative treatment for PD, an increasing number of studies have aimed at targeting this protein for therapeutics. Here, we reviewed and discussed the many different approaches that have been studied to inhibit α-syn accumulation via direct and indirect targeting. These analyses have led to the generation of multiple clinical trials that are either completed or currently active. These clinical trials and the current preclinical studies must still face obstacles ahead, but give hope of finding a therapy for PD with time.
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http://dx.doi.org/10.3390/biom10030391 | DOI Listing |
Alzheimers Dement
January 2025
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Background: We sought to characterize the cognitive profile among individuals with mild cognitive impairment with Lewy bodies (MCI-LB) to help guide future clinical criteria.
Methods: Systematic review and meta-analysis included MCI-LB studies with cognitive data from PubMed, Embase, Web of Science, and PsycINFO (January 1990 to March 2023). MCI-LB scores were compared to controls, MCI due to Alzheimer's disease (MCI-AD), and dementia with Lewy bodies (DLB) groups with random-effects models.
J Neural Transm (Vienna)
January 2025
Department of Neurology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University of College of Medicine, Seoul, Republic of Korea.
To investigate the clinical impact of mild behavioral impairment (MBI) in a predefined cohort with Lewy body disease (LBD) continuum. Eighty-four patients in the LBD continuum participated in this study, including 35 patients with video-polysomnography-confirmed idiopathic REM sleep behavior disorder (iRBD) and 49 clinically established LBD. Evaluations included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), neuropsychological tests, and MBI Checklist (MBI-C).
View Article and Find Full Text PDFDrug Deliv Transl Res
January 2025
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, 136119, Haryana, India.
Parkinson's disease (PD) is the most prominent and highly prevalent chronic neuro-degenerative disease generally recognized by classical motor symptoms which are linked with genetic mutation, Lewy bodies, and subsequently selective loss of nigrostriatal dopaminergic neurons. The blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier protect the central nervous system against toxins and are the most significant barriers to effective brain drug delivery in managing Parkinsonism. In recent years, intranasal delivery has attracted remarkable attention for brain targeting as the drug can be administered to the brain directly from the nose employing the trigeminal and olfactory pathways.
View Article and Find Full Text PDFJ Biomol Struct Dyn
January 2025
School of Medicine, Sari Branch, Islamic Azad University, Sari, Iran.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the formation of Lewy bodies, which are primarily composed of misfolded α-Synuclein (α-Syn). DJ-1 is a crucial protein involved in the correct folding of α-Syn, and mutations impairing its function are associated with the onset of PD. One such mutation, the L166P substitution in DJ-1, which has been linked to early-onset PD and results in the loss of DJ-1's homodimer structure.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
The predominant neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all of them share a combination of one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, and TAR DNA-binding protein 43. These toxic proteins share some common attributes, making them potentially universal and simultaneous targets for therapeutic intervention.
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