Article
Agriculture, Multidisciplinary
Wenqian Wang, Lili Qu, Zhan Cui, Fuping Lu, Li Li, Fufeng Liu
Summary: This study shows that the citrus flavonoid hesperetin (Hst) can inhibit the fibrillation of alpha-synuclein (alpha SN) and reduce its cytotoxicity, potentially serving as a dietary supplement to prevent the development of Parkinson's disease (PD).
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yu-Lin Guo, Wen-Jun Duan, Dan-Hua Lu, Xiao-Hui Ma, Xiao-Xiao Li, Zhao Li, Wei Bi, Hiroshi Kurihara, Hai-Zhi Liu, Yi-Fang Li, Rong-Rong He
Summary: GM1 ganglioside has therapeutic effects in experimental models of Parkinson's disease by promoting autophagy to clear harmful protein α-Syn, alleviating symptoms of neurodegenerative diseases like Parkinson's disease.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Biochemistry & Molecular Biology
Mazdak Afshar Bakshloo, Safia Yahiaoui, Matthieu Bourderioux, Regis Daniel, Manuela Pastoriza-Gallego, John J. Kasianowicz, Abdelghani Oukhaled
Summary: Alpha-synuclein plays a crucial role in regulating nerve activity. Mutations in this protein can lead to its aggregation and fibril formation, which is associated with neurodegenerative diseases like Parkinson's. Our study demonstrates that a nanometer-scale pore can effectively distinguish between different forms of alpha-synuclein, including wild-type, mutated, and post-translationally modified variants.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Cell Biology
Niharika Amireddy, Vandana Dulam, Shweta Kaul, Rajeswari Pakkiri, Shasi V. Kalivendi
Summary: Upregulation and aggregation of a-synuclein is a key factor in Parkinson's disease, and mitochondrial dysfunction is believed to be a contributing factor. The drug nitazoxanide has been found to enhance mitochondrial function and autophagy. This study demonstrates that nitazoxanide activates cellular autophagy and clears a-synuclein aggregates through mitochondrial uncoupling, AMPK activation, and JNK activation.
CELLULAR SIGNALLING
(2023)
Review
Biochemistry & Molecular Biology
Jennifer Ramirez, Samantha X. Pancoe, Elizabeth Rhoades, E. James Petersson
Summary: This article investigates the effects of interactions between the small neuronal protein alpha-synuclein and lipids on aggregation. By analyzing a comprehensive collection of experimental data, the general trends of lipid structure influencing aggregation are identified, providing a resource for interpreting the effects of lipids on aggregation and potentially serving as inputs for computational models.
Review
Biochemistry & Molecular Biology
Abbie T. Rodger, Maryam A. L. Nasser, Wayne G. Carter
Summary: Currently, there are no pharmacological treatments that can completely stop or reverse the progression of Parkinson's Disease (PD). Therefore, there is a need for neuroprotective therapies. This systematic review examines the effectiveness of anti-a-synuclein (a-syn) therapies in preventing PD progression in preclinical models and human clinical trials. The review found that novel preclinical anti-a-syn therapeutics reduced a-syn aggregations and protected against dopaminergic neuronal loss. Completed clinical trials showed significant tolerability and efficacy in reducing a-syn and minimal adverse effects. Overall, this review highlights the potential of anti-a-syn therapies in both preclinical and clinical settings to reduce a-syn accumulation and potentially slow down PD progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Jia Lu, Chenfei Wang, Xin Cheng, Ruizhi Wang, Xuehan Yan, Pengju He, Hongzhuan Chen, Zhihua Yu
Summary: The study suggests that modulating microglial metabolism and activating TRPV1 channels may be a promising therapeutic strategy for Parkinson's disease, as they can improve energy metabolism and attenuate neurodegeneration.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Nisha R. R. Dhanushkodi, Salema B. B. Abul Khair, Mustafa T. T. Ardah, M. Emdadul Haque
Summary: Mutations in ATP13A2 cause Kufor-Rakeb syndrome and affect the autophagic degradation of alpha-syn. Knocking down ATP13A2 in Drosophila results in increased levels of insoluble alpha-syn and decreased autophagic flux. ATP13A2 also affects dopaminergic neuron loss, sleep, and circadian activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiaoguang Liu, Kaluvu Balaraman, Ciaran C. Lynch, Michaeline Hebron, Priya Ketankumar Shah, Shicheng Hu, Max Stevenson, Christian Wolf, Charbel Moussa
Summary: The study found that Ubiquitin-Specific Protease-13 (USP13) plays a critical role in the neuropathology of alpha-synuclein and inhibiting USP13 can reduce alpha-synuclein levels and improve motor and behavioral symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Md Ezazul Haque, Mahbuba Akther, Shofiul Azam, In-Su Kim, Yuxi Lin, Young-Ho Lee, Dong-Kug Choi
Summary: In Parkinson's disease, the aggregated alpha-synuclein in Lewy bodies and mitochondrial dysfunction play crucial roles in neurodegeneration, with interactions between aggregated alpha-synuclein and mitochondria potentially leading to neuronal loss, making it an emerging drug target for Parkinson's disease treatment.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Erwan Bezard
Summary: This opinion paper addresses the issue of conceptual sloppiness and poor methodological characterization in Parkinson's disease research, emphasizing its negative impact on progress and proposing a remedy.
Article
Multidisciplinary Sciences
Dmitry Zenko, Jade Marsh, Andrew R. Castle, Rahel Lewin, Roman Fischer, George K. Tofaris
Summary: We developed a bimolecular fluorescence complementation assay to monitor de novo ubiquitination of alpha-synuclein, and identified lysine residues 45, 58, and 60 as critical sites for its degradation. The degradation involves NBR1 binding, entry into endosomes and subsequent lysosomal degradation. Our data also show the presence of ubiquitinated alpha-synuclein in Lewy bodies and cellular models of aggregation.
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
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)
Article
Chemistry, Multidisciplinary
Rongying Liu, Ran Zhang, Long Li, Zdravko Kochovski, Lintong Yao, Mu-Ping Nieh, Yan Lu, Tongfei Shi, Guosong Chen
Summary: This study reports a controlled fibril polymorphism library generated by designed glycopeptide building blocks and experimental and computational tools. The growth of fibrils, either axially or radially, is determined by a subtle balance of oligosaccharide and oligopeptide components, leading to right- or left-handed twisting structure. The study also provides visible evidence for the association process of double-strand fibrils, and demonstrates significant differences in macroscopic properties of fibril polymorphs on hydrogel formation and cellular migration control.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)