Article
Biochemistry & Molecular Biology
Edward Chau, Hyunjoo Kim, Jineun Shin, Alberto Martinez, Jin Ryoun Kim
Summary: The study found that AM17 can not only inhibit the aggregation of alpha S monomers, but also disaggregate alpha S oligomers and fibrils, independent of copper ions. Resveratrol also showed similar inhibitory effects on alpha S aggregation only in the presence of copper ions.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Joao D. Magalhaes, Emanuel Candeias, Ines Melo-Marques, Diana F. Silva, A. Raquel Esteves, Nuno Empadinhas, Sandra Morais Cardoso
Summary: Parkinson's disease is a neurodegenerative disease characterized by the loss of dopaminergic neurons. It has been found that autonomic symptoms and a-synuclein pathology in peripheral tissues are related in the early stage. By infecting the gut with Listeria monocytogenes, we observed oligomerization of a-synuclein in the ileum, along with a pro-inflammatory response and neuronal mitochondria dysfunction.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Afshan Iqbal, Fareeha Anwar, Uzma Saleem, Saira Sami Khan, Adnan Karim, Bashir Ahmad, Mubashra Gul, Zafer Iqbal, Tariq Ismail
Summary: This study found that Toco-D may be effective in improving locomotor activity and motor coordination in haloperidol-induced Parkinson's disease. Toco-D increased antioxidant enzyme and neurotransmitter levels, while decreasing inflammatory cytokine levels and mRNA expression of alpha-synuclein.
Article
Clinical Neurology
Jun Ueda, Norihito Uemura, Masanori Sawamura, Tomoyuki Taguchi, Masashi Ikuno, Seiji Kaji, Yosuke Taruno, Shuichi Matsuzawa, Hodaka Yamakado, Ryosuke Takahashi
Summary: This study found that the antiepileptic drug perampanel can inhibit the transmission of alpha-synuclein in neurons by blocking macropinocytosis dependent on neuronal activity, thus potentially serving as a novel disease-modifying drug for Parkinson's disease.
MOVEMENT DISORDERS
(2021)
Article
Neurosciences
Hengxing Zheng, Zhenhua Xie, Xuran Zhang, Jian Mao, Mengyuan Wang, Sijia Wei, Yiwen Fu, Hong Zheng, Ying He, Hui Chen, Yan Xu
Summary: This study examined the aggregation status, localization, and degradation characteristics of a-syn and p-a-syn in plasma exosomes from PD patients and healthy controls. Results indicated poor solubility of a-syn and p-a-syn after protease K treatment, with aggregates found inside and on the membrane surface of plasma exosomes. The ratios of oligomeric a-syn/total a-syn and oligomeric p-a-syn/total p-a-syn in plasma exosomes showed moderate utility in assisting PD diagnosis.
Article
Biochemistry & Molecular Biology
Tian-Zhong Hou, Hui-Min Yang, Yun-Zhong Cheng, Li Gu, Jian-Nan Zhang, Hong Zhang
Summary: This study investigates the potential link between Parkinson's disease and liver cancer, focusing on the role of exosome-delivered alpha-synuclein in inhibiting hepatocellular carcinoma (HCC) growth, migration, and invasion. Results show that exosomes containing alpha-synuclein from a Parkinson's disease cellular model suppress HCC development, and the abundance of Integrin alpha V beta 5 in these exosomes enhances their uptake by HCC cells.
MOLECULAR CARCINOGENESIS
(2023)
Article
Immunology
Ya-Nan Zhang, Jing-Kai Fan, Li Gu, Hui-Min Yang, Shu-Qin Zhan, Hong Zhang
Summary: The research demonstrated that mGluR5 inhibits alpha-synuclein-induced microglia inflammation to protect against neurotoxicity, while alpha-synuclein promotes the degradation of mGluR5 through lysosomal pathway to accelerate neuroinflammation. This novel mechanism may serve as a potential therapeutic target for Parkinson's disease.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Heejeong Kim, Han-Joo Maeng, Ji Hun Kim, Jin-Ha Yoon, Yohan Oh, Seung-Mann Paek, Yunjong Lee
Summary: The structural isomer trans-4'-acetyl-3'-tigloylkhellactone (racemic peucedanocoumarin IV [PCiv]) is found to effectively inhibit protein aggregation and has therapeutic potential in Parkinson's disease, with favorable pharmacokinetic properties and brain distribution.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Noah J. Graves, Yann Gambin, Emma Sierecki
Summary: Like many neurodegenerative diseases, Parkinson's disease (PD) is characterized by the formation of proteinaceous aggregates in brain cells. Additionally, these aggregates are also found in other disorders, collectively referred to as synucleinopathies. Despite the diversity in pathologies and symptoms, aSyn aggregates are a common marker and potential driver of these diseases. This review compares PD, DLB, and MSA, highlighting the role of aSyn aggregates in each disorder and discussing the relationship between aSyn strains and the cellular environment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Chang-Ki Oh, Nima Dolatabadi, Piotr Cieplak, Maria T. Diaz-Meco, Jorge Moscat, John P. Nolan, Tomohiro Nakamura, Stuart A. Lipton
Summary: This article investigates the mechanism by which dysregulation of autophagic pathways leads to the accumulation of abnormal proteins and damaged organdies in neurodegenerative disorders. The authors found that pathologic protein S-nitrosylation of p62 is a critical factor for autophagic inhibition and cell-to-cell spread.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Mahrokh Rezaei Kamelabad, Jaber Jahanbin Sardroodi, Alireza Rastkar Ebrahimzadeh, Marzieh Ajamgard
Summary: The study investigated the effects of two natural polyphenolic compounds, Curcumin (CUR) and Rosmarinic acid (RA), on disrupting the structure of α-Synuclein (α S) oligomers, which are believed to be related to Parkinson's disease pathology. The results showed that both compounds were successful in disrupting the original structure of α S oligomers, suggesting they could be suitable candidates for designing Parkinson's drugs.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2021)
Article
Cell Biology
Ye Peng, Jun-rui Ye, Sha-sha Wang, Wen-bin He, Zhong-ping Feng, Hong-shuo Sun, Shi-feng Chu, Zhao Zhang, Nai-hong Chen
Summary: The bibenzyl compound 20C derived from Gastrodia elata was found to inhibit the aggregation of A53T variants of alpha-synuclein directly in vitro. It displayed strong interaction with alpha-synuclein, reduced their beta-sheet structure, and reduced the amounts of alpha-synuclein inclusions in neural cells. In vivo experiments with A53T alpha-Syn transgenic mice showed that treatment with 20C significantly reduced toxic alpha-synuclein levels, improved behavioral performance, rescued dopaminergic neurons, and enhanced functional connections in the brain.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Pai-Yi Chiu, Fu-Chi Yang, Ming-Jang Chiu, Wei-Che Lin, Cheng-Hsien Lu, Shieh-Yueh Yang
Summary: This study investigated the combination of different biomarkers in AD, PD, and FTD and found that plasma biomarkers were consistent with pathology. This provides promise for the precise assessment of AD, PD, and FTD in clinical practice.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Salihu Mohammed, Isabella Russo, Ileana Ramazzina
Summary: A proteostasis network is a cellular system that controls the folding of functional proteins. Imbalance in proteostasis leads to an increase in misfolded proteins and the onset of diseases such as Parkinson's Disease. Molecular chaperones can counteract protein misfolding and aggregation, and modulation of their expression is a potential therapeutic strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Hayrettin Ozan Gulcan
Summary: Parkinson's disease (PD) is extensively studied in terms of its neuropathological background and treatment options. Current treatment strategies mainly focus on dopamine deficiency-related symptoms and involve dopaminergic agonists and compounds affecting dopamine metabolism. However, these drugs do not modify the disease, leading to alternative drug discovery studies targeting the progressive neurodegenerative characteristics of PD.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
