Article
Cell Biology
Hai-Yue Tu, Bao-Shi Yuan, Xiao-Ou Hou, Xiao-Jun Zhang, Chong-Shuang Pei, Ya-Ting Ma, Ya-Ping Yang, Yi Fan, Zheng-Hong Qin, Chun-Feng Liu, Li-Fang Hu
Summary: The extracellular transfer of alpha-Synuclein (alpha-Syn) contributes to Parkinson's disease pathogenesis by activating microglia and neuroinflammation. This study found that extracellular alpha-Syn inhibits microglia autophagy through Toll-like receptor 4 (Tlr4)-mediated p38 and Akt-mTOR signaling pathways, leading to neuroinflammation and PD development.
Review
Immunology
Yunna Li, Yun Xia, Sijia Yin, Fang Wan, Junjie Hu, Liang Kou, Yadi Sun, Jiawei Wu, Qiulu Zhou, Jinsha Huang, Nian Xiong, Tao Wang
Summary: Recent studies have shown that the excessive activation of microglia and release of pro-inflammatory cytokines play crucial roles in the pathogenesis and progression of Parkinson's disease (PD). The elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients exacerbates the pathology and accelerates disease progression. Current therapeutic drugs for PD primarily focus on relieving clinical symptoms, as there are no established strategies to stop or reverse the disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Johan Wallin, Per Svenningsson
Summary: Parkinson's disease is a neurodegenerative disorder with a significant immune component, both centrally and peripherally, indicating immunomodulation as a potential treatment strategy. The leukotriene pathway, specifically montelukast as a leukotriene receptor antagonist, shows promise as an anti-inflammatory treatment for PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Tingting Zheng, Zhengxiang Zhang
Summary: Parkinson's disease is characterized by the loss of dopaminergic neurons and abnormal aggregates of alpha-synuclein protein. There is currently no drug that can definitively slow down or stop its progression. The cell-to-cell transmission of pathologic alpha-synuclein seeds offers new treatment strategies, while neuroinflammation plays a crucial role in the development of alpha-synuclein pathology in PD.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Review
Cell Biology
Qian-Kun Lv, Kang-Xin Tao, Xiao-Bo Wang, Xiao-Yu Yao, Meng-Zhu Pang, Jun-Yi Liu, Fen Wang, Chun-Feng Liu
Summary: Parkinson's disease is a common neurodegenerative disease characterized by the accumulation of alpha-synuclein in microglia, leading to neuroinflammation. The autophagy and phagocytosis functions of microglia are related to the clearance of alpha-synuclein and the inhibition of neuroinflammation. This review discusses the interaction between microglia and alpha-synuclein in Parkinson's disease pathogenesis, and the possible mechanisms of microglial autophagy and phagocytosis in the clearance of alpha-synuclein and inhibition of neuroinflammation.
INFLAMMATION RESEARCH
(2023)
Article
Neurosciences
Savannah M. Rocha, Kelly S. Kirkley, Debotri Chatterjee, Tawfik A. Aboellail, Richard J. Smeyne, Ronald B. Tjalkens
Summary: Parkinson's disease is the most common neurodegenerative movement disorder worldwide, with a higher prevalence in men. The cause of the disease is largely unknown, but environmental exposures and neuroinflammation are linked to the misfolding of proteins and disease progression. Activated microglia play a role in promoting neuroinflammation in Parkinson's disease, but the interaction between environmental agents and specific innate immune signaling pathways in microglia is not well understood.
Review
Clinical Neurology
Ashley S. Harms, Sara A. Ferreira, Marina Romero-Ramos
Summary: Parkinson's disease involves both neuronal events and a significant immune component, with changes in the immune system occurring in both the central nervous system and the periphery. Alpha-synuclein plays a crucial role in activating the innate and adaptive immune system, contributing to neuronal degeneration and symptomatology in patients.
ACTA NEUROPATHOLOGICA
(2021)
Article
Immunology
Adrianne F. Pike, Francesca Longhena, Gaia Faustini, Jean-Marc Van Eik, Iris Gombert, Maaike A. C. Herrebout, Mona M. H. E. Fayed, Michele Sandre, Tatiana Varanita, Charlotte E. Teunissen, Jeroen J. M. Hoozemans, Arianna Bellucci, Robert Veerhuis, Luigi Bubacco
Summary: This study reveals that dopamine inhibits the activation of NLRP3 inflammasome in primary human microglia, providing insights into the potential therapeutic target for Parkinson's disease.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Neurosciences
Fan Zhang, Zhiwei Wu, Fei Long, Jieqiong Tan, Ni Gong, Xiaorong Li, Changwei Lin
Summary: This article summarizes the effects of ATP13A2 gene mutations on PD, discusses the molecular mechanism of lysosomal autophagy inhibition and abnormal alpha-synuclein accumulation, and provides a new direction for future research on the pathogenesis and therapeutic targets of ATP13A2 gene-related PD.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Medicine, Research & Experimental
Qianhui Huang, Pei Yang, Yang Liu, Jianhua Ding, Ming Lu, Gang Hu
Summary: Alpha-Synuclein, a member of the synuclein protein family, plays an important role in the formation and transmission of nerve synapses. Its abnormal aggregation is recognized as one of the important factors leading to neuroinflammation in Parkinson's disease. This study investigated the influence of post translational modification of alpha-Syn on its pathological aggregation and summarized various pathways that activate NLRP3 triggered by alpha-Syn and targeted therapeutic strategies.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Huiling Gao, Hehong Sun, Nan Yan, Pu Zhao, He Xu, Wei Zheng, Xiaoyu Zhang, Tao Wang, Chuang Guo, Manli Zhong
Summary: Zinc homeostasis imbalance is a major cause of Parkinson's disease, and ATP13A2 plays an important role in regulating zinc homeostasis and alpha-synuclein accumulation. High zinc ion treatment leads to reduced spatial exploration behavior in mice, increased phosphorylation levels of alpha-synuclein, inhibition of the autophagy pathway, and activation of apoptosis signaling pathways. Overexpression of ATP13A2 reverses these protein changes, while its knockout exacerbates alpha-synuclein phosphorylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Gregory P. Williams, Aubrey M. Schonhoff, Asta Jurkuvenaite, Nicole J. Gallups, David G. Standaert, Ashley S. Harms
Summary: Alpha-synuclein is implicated in the activation of the immune system in Parkinson's disease, leading to T cell responses and infiltration into the CNS. Genetic deletion or using immunosuppressive drugs can reduce these damaging T cell responses, suggesting a potential avenue for disease-modifying treatments targeting the immune activation associated with alpha-synuclein pathology.
Article
Neurosciences
Matthew E. Gegg, Elisa Menozzi, Anthony H. V. Schapira
Summary: Dysfunction of the endolysosomal system is associated with the pathogenesis of Parkinson's disease (PD), and genetic variants in the GBA gene are a common risk factor. GCase deficiency in neurons and glia may contribute to PD by promoting the accumulation and spread of alpha-synuclein aggregates. Dysregulation of lipids, including sphingolipids, phospholipids, and cholesterol, as well as neuroinflammation and the interaction between GCase and LRRK2 protein, are also implicated in PD pathogenesis.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Clinical Neurology
Tai Wang, Changhe Shi, Haiyang Luo, Huimin Zheng, Liyuan Fan, Mibo Tang, Yun Su, Jing Yang, Chengyuan Mao, Yuming Xu
Summary: Parkinson's disease is a heterogeneous neurodegenerative disease involving neuroinflammation as a common factor. This review highlights the relationship between the common pathological mechanisms of PD and neuroinflammation, discussing the role of the immune system in the pathogenesis of PD.
Review
Cell Biology
Eddie Pradas, Marta Martinez-Vicente
Summary: GBA gene variants are the first genetic risk factor for Parkinson's disease. GBA encodes the lysosomal enzyme glucocerebrosidase (GBA), which is involved in sphingolipid metabolism. The loss of GBA activity has been associated with the accumulation of alpha-synuclein species.
Article
Clinical Neurology
Sneha Pandya, Ulrike W. Kaunzner, Sandra M. Hurtado Rua, Nancy Nealon, Jai Perumal, Timothy Vartanian, Thanh D. Nguyen, Susan A. Gauthier
JOURNAL OF NEUROIMAGING
(2020)
Article
Neurosciences
Jana Ivanidze, Myrto Skafida, Sneha Pandya, Dylon Patel, Joseph R. Osborne, Ashish Raj, Ajay Gupta, Claire Henchcliffe, Jonathan P. Dyke
FRONTIERS IN NEUROSCIENCE
(2020)
Article
Radiology, Nuclear Medicine & Medical Imaging
Mercy I. Akerele, Sara A. Zein, Sneha Pandya, Anastasia Nikolopoulou, Susan A. Gauthier, Ashish Raj, Claire Henchcliffe, P. David Mozley, Nicolas A. Karakatsanis, Ajay Gupta, John Babich, Sadek A. Nehmeh
Summary: The study aimed to assess the reproducibility of [C-11]DPA-713 PET kinetic analysis using population-based input function (PBIF) and potentially eliminate the need for arterial input functions (AIF). The results showed that PBIF-based kinetic modeling is clinically feasible and can be an alternative to PSAIF, with variability in V-T within that obtained for test-retest studies.
Article
Clinical Neurology
Sandra M. Hurtado Rua, Ulrike W. Kaunzner, Sneha Pandya, Elizabeth Sweeney, Ceren Tozlu, Amy Kuceyeski, Thanh D. Nguyen, Susan A. Gauthier
Summary: The study analyzed MS patients using MRI features and grouped them into two distinct patient clusters. Lesion MWF and volume distribution played a significant role in cluster formation, which was associated with patient EDSS evaluations.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Behavioral Sciences
Ceren Tozlu, Keith Jamison, Thanh Nguyen, Nicole Zinger, Ulrike Kaunzner, Sneha Pandya, Yi Wang, Susan Gauthier, Amy Kuceyeski
Summary: In patients with multiple sclerosis, lesions with a hyperintense rim on QSM are associated with greater myelin damage and disability, and rim+ lesions may have a stronger impact on disability through disruptions to structural connectivity. This study provides insights into the mechanisms underlying MS-related disability.
BRAIN AND BEHAVIOR
(2021)
Article
Clinical Neurology
Yeona Kang, Sneha Pandya, Nicole Zinger, Nara Michaelson, Susan A. Gauthier
Summary: The pilot study identified that innate immune activity may increase over time in patients with progressive MS, with a focus on PK11195 uptake in NAWM, cortex, thalamus, and putamen.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Neurosciences
Sneha Pandya, Pedro D. Maia, Benjamin Freeze, Ricarda A. L. Menke, Kevin Talbot, Martin R. Turner, Ashish Raj
Summary: The study used a computational model to demonstrate a structural network-based regional pathological spread in ALS, with no simple relationship to the spatial distribution of ALS-related genes in the healthy brain. The OPTN gene was identified as a significant but weaker non-NDM contributor in the network-gene interaction model, with critical seed regions for spread within the model located in the basal ganglia, thalamus, and insula.
Article
Clinical Neurology
Pedro D. Maia, Sneha Pandya, Benjamin Freeze, Justin Torok, Ajay Gupta, Yashar Zeighami, Ashish Raj
BRAIN COMMUNICATIONS
(2020)
Article
Clinical Neurology
Benjamin Freeze, Pedro Maia, Sneha Pandya, Ashish Raj
BRAIN COMMUNICATIONS
(2020)
Meeting Abstract
Clinical Neurology
Neha Safi, Sneha Pandya, Thanh Nguyen, Weiyuan Huang, Ulrike Kaunzner, Nancy Nealon, Jai Perumal, Timothy Vartanian, Yi Wang, Susan Gauthier
Meeting Abstract
Clinical Neurology
N. Safi, S. Pandya, T. Nguyen, U. W. Kaunzner, N. Nealon, J. Perumal, T. Vartanian, Y. Wang, S. Gauthier
MULTIPLE SCLEROSIS JOURNAL
(2020)
Meeting Abstract
Clinical Neurology
C. Tozlu, S. Zhang, T. Nguyen, N. Nealon, J. Perumal, T. Vartanian, E. Morris, U. W. Kaunzner, S. Pandya, Y. Wang, S. Gauthier, A. Kuceyeski
MULTIPLE SCLEROSIS JOURNAL
(2020)
Meeting Abstract
Clinical Neurology
C. Tozlu, S. Zhang, T. Nguyen, N. Nealon, J. Perumal, T. Vartanina, E. Morris, U. Kaunzner, S. Pandya, Y. Wang, S. Gauthier, A. Kuceyeski
MULTIPLE SCLEROSIS JOURNAL
(2019)
Article
Clinical Neurology
S. Zhang, T. D. Nguyen, S. M. Hurtado Rua, U. W. Kaunzner, S. Pandya, I. Kovanlikaya, P. Spincemaille, Y. Wang, S. A. Gauthier
AMERICAN JOURNAL OF NEURORADIOLOGY
(2019)
Meeting Abstract
Clinical Neurology
Yeona Kang, Ulrike Kaunzner, Sneha Pandya, Amy Kuceyesky, Nancy Nealon, Jai S. Perumal, Timothy Vartanian, Susan Gauthier
MULTIPLE SCLEROSIS JOURNAL
(2019)