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)
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)
Review
Biochemistry & Molecular Biology
Rubina Roy, Rajib Paul, Pallab Bhattacharya, Anupom Borah
Summary: Parkinson's disease is a neurodegenerative disease that causes dopamine depletion and motor deficits. Nanovesicle technology has advantages in delivering drugs to the target site, leading to improved therapeutic efficacy. Multiple drug-carrying abilities of nanovesicles have also shown success in targeting different pathological events of PD.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Guiqin Chen, Eun Hee Ahn, Seong Su Kang, Yiyuan Xia, Xia Liu, Zhaohui Zhang, Keqiang Ye
Summary: This study demonstrates that AEP cleavage of UNC5C receptor contributes to dopaminergic neuronal loss in Parkinson's disease (PD), and the fragmentation of UNC5C is inversely correlated with reduced netrin-1 levels.
Review
Medicine, General & Internal
E. Srinivasan, G. Chandrasekhar, P. Chandrasekar, K. Anbarasu, A. S. Vickram, Rohini Karunakaran, R. Rajasekaran, P. S. Srikumar
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons, with pathogenesis linked to the misfolding and mutations of alpha-synuclein protein. Genetic and other factors lead to the formation of amyloid structures from alpha-synuclein, causing PD.
FRONTIERS IN MEDICINE
(2021)
Article
Medicine, Research & Experimental
Colleen S. Stein, Jared M. McLendon, Nathan H. Witmer, Ryan L. Boudreau
Summary: Parkinson's disease is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. The pathogenesis of PD involves perturbations in gene regulation, mitochondrial function, and neuronal activity. Studies have shown that miR-181 expression is altered in PD brains, and it can regulate genes related to synaptic transmission, neurite outgrowth, and mitochondrial respiration.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Pharmacology & Pharmacy
Samuel Pena-Diaz, Javier Garcia-Pardo, Salvador Ventura
Summary: Parkinson's disease is the second most common neurodegenerative disorder worldwide, characterized by protein deposits in dopaminergic neurons. Recent research has identified compounds primarily of an aromatic nature that target a-Syn aggregation. This study provides a historical overview of Parkinson's disease, its molecular aspects, and current trends in small compound development to address a-Syn aggregation. These compounds are promising for the development of effective therapies for Parkinson's disease.
Article
Medicine, General & Internal
G. Pagano, K. I. Taylor, J. Anzures-Cabrera, M. Marchesi, T. Simuni, K. Marek, R. B. Postuma, N. Pavese, F. Stocchi, J. -P. Azulay, B. Mollenhauer, L. Lopez-Manzanares, D. S. Russell, J. T. Boyd, A. P. Nicholas, M. R. Luquin, R. A. Hauser, T. Gasser, W. Poewe, B. Ricci, A. Boulay, A. Vogt, F. G. Boess, J. Dukart, G. D'Urso, R. Finch, S. Zanigni, A. Monnet, N. Pross, A. Hahn, H. Svoboda, M. Britschgi, F. Lipsmeier, E. Volkova-Volkmar, M. Lindemann, S. Dziadek, S. Holiga, D. Rukina, T. Kustermann, G. A. Kerchner, P. Fontoura, D. Umbricht, R. Doody, T. Nikolcheva, A. Bonni
Summary: The study found that prasinezumab had no meaningful effect on global or imaging measures of Parkinson's disease progression and was associated with infusion reactions.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Ezia Guatteo, Nicola Berretta, Vincenzo Monda, Ada Ledonne, Nicola Biagio Mercuri
Summary: This article focuses on the functional properties of nigral dopaminergic neurons and summarizes the shared or unique features of neuronal dysfunction in different stages of PD animal models, with the goal of illustrating the functional modifications occurring in these neurons during disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fiamma A. Buratti, Claudio Oscar Fernandez, Markus Zweckstetter
Summary: Parkinson's disease can be either sporadic or inherited, with missense mutations causing the inherited form. The V15A mutation of alpha-synuclein weakens its affinity for membranes but does not significantly affect its conformation in solution. This leads to increased concentration of aggregation-prone alpha-synuclein, allowing the V15A variant to form amyloid fibrils. These findings underscore the importance of maintaining a balance between membrane-bound and free aggregation-competent alpha-synuclein in synucleinopathies.
Review
Biochemistry & Molecular Biology
Maxime Teixeira, Razan Sheta, Walid Idi, Abid Oueslati
Summary: The abnormal accumulation of alpha-synuclein into proteinaceous inclusions called Lewy bodies is a neuropathological hallmark of Parkinson's disease and related disorders. Emerging evidence suggests that dysfunction of the endolysosomal system may play a role in the formation of these inclusions. The interaction between alpha-synuclein aggregation and the endolysosomal system disruption is not fully understood, but it is a potential target for developing disease-modifying treatments for PD and related disorders.
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)
Article
Multidisciplinary Sciences
Takuto Fujii, Shushi Nagamori, Pattama Wiriyasermkul, Shizhou Zheng, Asaka Yago, Takahiro Shimizu, Yoshiaki Tabuchi, Tomoyuki Okumura, Tsutomu Fujii, Hiroshi Takeshima, Hideki Sakai
Summary: Mutations in the human ATP13A2 gene are associated with the development of Parkinson's disease. This study reveals that ATP13A2 acts as a H+/K+ transporting protein in lysosomes, which prevents alkalization of lysosomes and accumulation of alpha-synuclein.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Irena Hlushchuk, Justyna Barut, Mikko Airavaara, Kelvin Luk, Andrii Domanskyi, Piotr Chmielarz
Summary: This study is the first attempt to investigate the direct effects of insulin signaling on pathological alpha-synuclein accumulation in dopamine neurons. The results suggest that modifying insulin signaling does not significantly affect alpha-synuclein aggregation, but the choice of culturing media can significantly affect preformed fibril-induced alpha-synuclein phosphorylation in dopamine neurons.
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.
Article
Multidisciplinary Sciences
Hyojung Kim, Seok-Jae Kang, Young Mi Jo, Min Song Kim, Yunjong Lee, Seok-Hyun Cho, Hee-Tae Kim
SCIENTIFIC REPORTS
(2019)
Article
Medicine, General & Internal
Areum Jo, Yunjong Lee, Chi-Hu Park, Joo-Ho Shin
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Multidisciplinary Sciences
Hee Sook Bae, Yun-Kyeong Jin, Sangwoo Ham, Hee Kyoung Kim, Hyejung Shin, Gyu-bon Cho, Kyu Jun Lee, Hohyeon Lee, Kyeong-Min Kim, Ok-Jae Koo, Goo Jang, Jung Min Lee, Jae Young Lee
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Hyojung Kim, Jisoo Park, Hojin Kang, Seung Pil Yun, Yun-Song Lee, Yun-Il Lee, Yunjong Lee
Article
Cell Biology
Areum Jo, Yunjong Lee, Tae-In Kam, Sung-Ung Kang, Stewart Neifert, Senthilkumar S. Karuppagounder, Rin Khang, Hojin Kang, Hyejin Park, Shih-Ching Chou, Sungtaek Oh, Haisong Jiang, Deborah A. Swing, Sangwoo Ham, Sheila Pirooznia, George K. E. Umanah, Xiaobo Mao, Manoj Kumar, Han Seok Ko, Ho Chul Kang, Byoung Dae Lee, Yun-Il Lee, Shaida A. Andrabi, Chi-Hu Park, Ji-Yeong Lee, Hanna Kim, Hyein Kim, Hyojung Kim, Jin Whan Cho, Sun Ha Paek, Chan Hyun Na, Lino Tessarollo, Valina L. Dawson, Ted M. Dawson, Joo-Ho Shin
Summary: Accumulation of parkin-interacting substrate (PARIS) due to inactivation of parkin contributes to Parkinson's disease (PD) through repression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) activity. Farnesol, identified as an inhibitor of PARIS, promotes farnesylation of PARIS and prevents its repression of PGC-1 alpha by reducing PARIS occupancy on the PPARGC1A promoter. Studies show that farnesol can prevent dopaminergic neuronal loss and behavioral deficits by enhancing PARIS farnesylation, suggesting a potential therapeutic role in PD treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Anusha Balla, Yoo-Seong Jeong, Hyo-Jung Kim, Yun-Jong Lee, Suk-Jae Chung, Yoon-Jee Chae, Han-Joo Maeng
Summary: In this study, the impact of 1,25(OH)(2)D-3 on the expression of rat OCTs and MATEs was investigated, revealing significant changes in mRNA expression in various tissues. The alteration of pharmacokinetics of procainamide and N-acetyl procainamide in the presence of 1,25(OH)(2)D-3 was also observed, demonstrating a physiological model for linking changes in transporter expression to drug pharmacokinetics.
Article
Toxicology
Sangwoo Ham, Ji Hun Kim, Heejeong Kim, Jeong-Yong Shin, Yunjong Lee
Summary: The iron chelator deferasirox enhances parkin expression and provides cytoprotection against oxidative stress through the PERK-ATF4 pathway.
TOXICOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Mina Yeom, Jin-Kyung Hong, Joo-Ho Shin, Yunjong Lee, Frederick Peter Guengerich, Jeong-Yun Choi
Summary: Three variants of DNA polymerase, C34W, I147N, and R167Q, have been found to significantly decrease the repair function of cells, leading to increased sensitivity to UV radiation and cisplatin chemotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hojin Kang, Soojeong Park, Areum Jo, Xiaobo Mao, Manoj Kumar, Chi-Hu Park, Jee-Yin Ahn, Yunjong Lee, Jeong-Yun Choi, Yun-Song Lee, Valina L. Dawson, Ted M. Dawson, Tae-In Kam, Joo-Ho Shin
Summary: PARIS undergoes liquid-liquid phase separation (LLPS) and amorphous solid formation in Parkinson's disease. The N-terminal low complexity domain 1 (LCD1) is required for LLPS, while the C-terminal prion-like domain (PrLD) drives the transition from liquid to solid phase. In addition, poly(ADP-ribose) (PAR) accelerates the LLPS and solidification of PARIS.
Article
Biochemistry & Molecular Biology
Hyojung Kim, Jeong-Yong Shin, Yun-Song Lee, Seung Pil Yun, Han-Joo Maeng, Yunjong Lee
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Sangwoo Ham, Seung Pil Yun, Hyojung Kim, Donghoon Kim, Bo Am Seo, Heejeong Kim, Jeong-Yong Shin, Mohamad Aasif Dar, Gum Hwa Lee, Yun Il Lee, Doyeun Kim, Sunghoon Kim, Hee-Seok Kweon, Joo-Ho Shin, Han Seok Ko, Yunjong Lee
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Sangwoo Ham, Hyojung Kim, Seojin Hwang, Hyunook Kang, Seung Pil Yun, Sangjune Kim, Donghoon Kim, Hyun Sook Kwon, Yun-Song Lee, MyoungLae Cho, Heung-Mook Shin, Heejung Choi, Ka Young Chung, Han Seok Ko, Gum Hwa Lee, Yunjong Lee
MOLECULES AND CELLS
(2019)