Unravelling LRRK2 pathways in Parkinson's disease: Mechanisms and intricacies

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as tremors, stiffness, and bradykinesia, as well as non-motor symptoms like cognitive impairment and mood swings. PD is a multifactorial disease comprised of environmental and genetic etiologies. In addition to family history, Variants in the LRRK2 gene are important as they represent the most common cause of familial PD and are also associated with some sporadic cases. The underlying causes of PD are also numerous and can be divided into a variety of environmental and genetic factors. This is the most relevant part because the LRRK2 gene Variant is one of the most common causes of familial Parkinson's disease, as well as contributing to sporadic cases beyond hereditary factors. Pathogenic LRRK2 variants result in the dysfunction of LRRK2, disrupting cellular pathways and potentially driving neurodegeneration. The purpose of the current study was to examine in depth the complex network of LRRK2-regulated signalling pathways and how they collectively modulate changes in neuronal survival and function. These LRRK2 variants are causing cell homeostasis disturbances due to dysfunction of interaction between key proteins such as ?-synuclein and tau that have been implicated in Parkinson's development. In addition, we will explore what other therapies could be targeted to mitigate the role of LRRK2-mediated processes in PD, such as kinase inhibitors and other process-targeted treatments.