TY - JOUR
T1 - The multifaceted role of LRRK2 in Parkinson's disease
T2 - From human iPSC to organoids
AU - Oun, Asmaa
AU - Sabogal-Guaqueta, Angelica Maria
AU - Galuh, Sekar
AU - Alexander, Anastasia
AU - Kortholt, Arjan
AU - Dolga, Amalia M
N1 - Copyright © 2022. Published by Elsevier Inc.
PY - 2022/10/15
Y1 - 2022/10/15
N2 - Parkinson's disease (PD) is the second most common neurodegenerative disease affecting elderly people. Pathogenic mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are the most common cause of autosomal dominant PD. LRRK2 activity is enhanced in both familial and idiopathic PD, thereby studies on LRRK2-related PD research are essential for understanding PD pathology. Finding an appropriate model to mimic PD pathology is crucial for revealing the molecular mechanisms underlying disease progression, and aiding drug discovery. In the last few years, the use of human-induced pluripotent stem cells (hiPSCs) grew exponentially, especially in studying neurodegenerative diseases like PD, where working with brain neurons and glial cells was mainly possible using postmortem samples. In this review, we will discuss the use of hiPSCs as a model for PD pathology and research on the LRRK2 function in both neuronal and immune cells, together with reviewing the recent advances in 3D organoid models and microfluidics.
AB - Parkinson's disease (PD) is the second most common neurodegenerative disease affecting elderly people. Pathogenic mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are the most common cause of autosomal dominant PD. LRRK2 activity is enhanced in both familial and idiopathic PD, thereby studies on LRRK2-related PD research are essential for understanding PD pathology. Finding an appropriate model to mimic PD pathology is crucial for revealing the molecular mechanisms underlying disease progression, and aiding drug discovery. In the last few years, the use of human-induced pluripotent stem cells (hiPSCs) grew exponentially, especially in studying neurodegenerative diseases like PD, where working with brain neurons and glial cells was mainly possible using postmortem samples. In this review, we will discuss the use of hiPSCs as a model for PD pathology and research on the LRRK2 function in both neuronal and immune cells, together with reviewing the recent advances in 3D organoid models and microfluidics.
U2 - 10.1016/j.nbd.2022.105837
DO - 10.1016/j.nbd.2022.105837
M3 - Review article
C2 - 35963526
SN - 0969-9961
VL - 173
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 105837
ER -