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2000
Volume 24, Issue 11
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease worldwide and presents as a progressive motor disorder. Gene mutations play a pivotal role in the degeneration of dopaminergic neurons in the substantia nigra region. Mutations in the Leucine rich repeat kinase 2 (LRRK2) gene have been identified as one of the most common genetic causes of PD. LRRK2 is a multi-functional protein involved in several critical cellular processes, including mitochondrial function, autophagy, vesicular trafficking, and immune system regulation. Dysregulation of these processes due to aberrant LRRK2 activity contributes to neuronal degeneration, particularly in dopaminergic neurons, which are most affected in PD. The current review discusses the structure of LRRK2, its function, and pathogenic mutations in the context of PD. However, significant challenges remain, particularly in terms of ensuring drug specificity, minimizing off-target effects, and understanding the long-term safety and efficacy of these treatments. As we advance our understanding of LRRK2 biology, it remains a highly promising target for therapeutic strategies aimed at modifying the course of Parkinson’s disease.

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2025-12-16

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Exploring LRRK2-dependent Mechanisms in Parkinson’s Disease Therapy
CNS Neurol. Disord. Drug Targets 24, 823 (2025); https://doi.org/10.2174/0118715273377507250320035243
/content/journals/cnsnddt/10.2174/0118715273377507250320035243
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  • Article Type:     Review Article
Keyword(s): leucine rich repeat kinase 2; LRRK2 mutations; mitochondrial dysfunction; neurodegeneration; Parkinson’s disease; vesicle trafficking; α-synuclein

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