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
Clinical Neurology
Tommaso Schirinzi, Daniela Maftei, Francesco M. Passali, Piergiorgio Grillo, Henri Zenuni, Davide Mascioli, Riccardo Maurizi, Laura Loccisano, Martina Vincenzi, Anna Maria Rinaldi, Massimo Ralli, Stefano Di Girolamo, Alessandro Stefani, Roberta Lattanzi, Cinzia Severini, Nicola B. Mercuri
Summary: This study outlines the dynamics of the prokineticin-2 pathway in relation to the clinical-pathological features of Parkinson's disease by examining olfactory neurons of patients. The results show that prokineticin-2 expression is increased in Parkinson's disease and is directly correlated with the severity of motor symptoms. Additionally, the accumulation of oligomeric alpha-synuclein is associated with prokineticin-2 protein levels. These findings support prokineticin-2 as a potential target for Parkinson's disease and validate the use of olfactory neurons to reflect pathological changes of the disease.
ANNALS OF NEUROLOGY
(2023)
Article
Neurosciences
Ross D. Markello, Golia Shafiei, Christina Tremblay, Ronald B. Postuma, Alain Dagher, Bratislav Misic
Summary: Individuals with Parkinson's disease exhibit a complex clinical phenotype, where data fusion can capture inter-dependencies among different modalities, with neuroimaging data playing a critical role.
NPJ PARKINSONS DISEASE
(2021)
Review
Immunology
Manlian Zhu, Xia Liu, Yiru Ye, Xiumei Yan, Yiwen Cheng, Longyou Zhao, Feng Chen, Zongxin Ling
Summary: Parkinson's disease is a common neurodegenerative disease characterized by motor dysfunction. Gut dysbiosis is involved in the development and progression of PD, and the gut microbiota can be considered as a potential diagnostic and therapeutic target. Gut dysbiosis influences the progression and onset of PD by increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels of alpha-synuclein fibrils, increasing oxidative stress, and decreasing neurotransmitter production.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Clinical Neurology
Johannes Burtscher, Muhammed Muazzam Kamil Syed, Hilal A. Lashuel, Gregoire P. Millet
Summary: Several lines of research suggest that low oxygen supply plays a key role in the pathogenesis of Parkinson's disease. While severe hypoxia is harmful for the brain, physiological adaptations to mild hypoxia are neuroprotective. The discussion focuses on how neuroprotective effects can be induced through hypoxia conditioning and potentially used as therapeutic strategies for Parkinson's disease.
MOVEMENT DISORDERS
(2021)
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
Clinical Neurology
Chukwunonso K. Nwabufo, Omozojie P. Aigbogun
Summary: The development of disease-modifying drugs and differential diagnostic agents is urgently needed in Parkinson's disease, with the misfolding of alpha-synuclein being identified as a potential biomarker. Finding the most appropriate diagnostic modality based on alpha-synuclein could revolutionize the diagnosis of Parkinson's. Molecules targeting alpha-synuclein may alter the disease pathway leading to Parkinson's.
JOURNAL OF NEUROLOGY
(2022)
Review
Neurosciences
Scott G. Allen, Richard M. Meade, Lucy L. White Stenner, Jody M. Mason
Summary: Peptides and their mimetics have been recognized as important drug-like molecules for inhibiting intracellular protein-protein interactions. Evidence has shown the involvement of misfolding and aggregation of alpha-synuclein in the onset and progression of Parkinson's disease and related synucleinopathies. Developing peptides and their mimetics to directly engage with alpha-synuclein and modulate aggregation and toxicity holds promise for therapeutic interventions and early diagnosis.
MOLECULAR NEURODEGENERATION
(2023)
Editorial Material
Immunology
Youcui Wang, Xiaoqin Zhang, Fenghua Chen, Leilei Chen, Jun Wang, Junxia Xie
Summary: Neuroinflammation is crucial in the pathogenesis of Parkinson's disease. Modulation of the LRRK2-NFATc2 signaling cascade in microglia could be a potential therapeutic target for PD treatment. The activation of LRRK2 by neuron-released alpha-synuclein via TLR2 leads to a neurotoxic inflammatory environment.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Cell Biology
Jea-Young Lee, Zhen-Jie Wang, Alexa Moscatello, Chase Kingsbury, Blaise Cozene, Jeffrey Farooq, Madeline Saft, Nadia Sadanandan, Bella Gonzales-Portillo, Henry Zhang, Felipe Esparza Salazar, Alma Rosa Lezama Toledo, German Rivera Monroy, Reed Berlet, Cyndy D. Sanberg, Paul R. Sanberg, Cesario Borlongan
Summary: This study focuses on the role of the gut-brain axis in Parkinson's disease (PD) pathology and treatment. The researchers found that gut dysbiosis is a major pathological source of PD and that transplantation of stem cells and plasma derived from human umbilical cord blood can ameliorate the symptoms of PD. In addition, the study also revealed the inflammatory signals and alpha-synuclein overload in the gut and the brain, which could be reduced through transplantation. Overall, this study highlights the importance of the gut-brain axis in PD and provides potential therapeutic targets.
CELL DEATH DISCOVERY
(2022)
Article
Medicine, Research & Experimental
Lena F. Burbulla, Jianbin Zheng, Pingping Song, Weilan Jiang, Michaela E. Johnson, Patrik Brundin, Dimitri Krainc
Summary: Current treatments for Parkinson's disease only provide symptomatic relief, but repurposing FDA-approved drugs such as quetiapine as a modulator of GCase activity shows potential for improving the condition of PD patients with decreased GCase activity. This study developed an efficient screening strategy for identifying drugs to treat PD and found that quetiapine treatment could increase levels and activity of wild-type GCase and reduce the accumulation of oxidized dopamine, glucosylceramide, and alpha-synuclein in PD patients.
Article
Neurosciences
Sijia Yin, Chao Han, Yun Xia, Fang Wan, Junjie Hu, Liang Kou, Yadi Sun, Jiawei Wu, Yunna Li, Qiulu Zhou, Nian Xiong, Jinsha Huang, Tao Wang
Summary: This study identified and validated cancerous inhibitor of PP2A (CIP2A) as a potential diagnostic biomarker for Parkinson's disease (PD). The results showed that plasma CIP2A concentrations were significantly lower in PD patients compared to controls, and CIP2A played a role in PD-related pathogenesis in cellular and mouse models. This suggests that CIP2A could be a novel biomarker for PD.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Bei Huang, Steven W. H. Chau, Yaping Liu, Joey W. Y. Chan, Jing Wang, Suk Ling Ma, Jihui Zhang, Paul K. S. Chan, Yun Kit Yeoh, Zigui Chen, Li Zhou, Sunny Hei Wong, Vincent C. T. Mok, Ka Fai To, Hei Ming Lai, Simon Ng, Claudia Trenkwalder, Francis K. L. Chan, Yun Kwok Wing
Summary: The study reveals that the gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. The depletion of butyrate-producing bacteria and the enrichment of pro-inflammatory Collinsella have emerged in RBD and RBD-FDR after controlling potential confounders. The study also identifies 12 microbial markers that can effectively distinguish RBD from control.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Eleanor Sinclair, Drupad K. Trivedi, Depanjan Sarkar, Caitlin Walton-Doyle, Joy Milne, Tilo Kunath, Anouk M. Rijs, Rob M. A. de Bie, Royston Goodacre, Monty Silverdale, Perdita Barran
Summary: This study used metabolomics profiling to identify changes in lipids in the sebum of PD patients, with alterations related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism, and fatty acid biosynthesis. The findings suggest sebum can be a potential source for identifying biomarkers for PD.
NATURE COMMUNICATIONS
(2021)
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
Nidhi Sahni, Song Yi, Mikko Taipale, Juan I. Fuxman Bass, Jasmin Coulombe-Huntington, Fan Yang, Jian Peng, Jochen Weile, Georgios I. Karras, Yang Wang, Istvan A. Kovacs, Atanas Kamburov, Irina Krykbaeva, Mandy H. Lam, George Tucker, Vikram Khurana, Amitabh Sharma, Yang-Yu Liu, Nozomu Yachie, Quan Zhong, Yun Shen, Alexandre Palagi, Adriana San-Miguel, Changyu Fan, Dawit Balcha, Amelie Dricot, Daniel M. Jordan, Jennifer M. Walsh, Akash A. Shah, Xinping Yang, Ani K. Stoyanova, Alex Leighton, Michael A. Calderwood, Yves Jacob, Michael E. Cusick, Kourosh Salehi-Ashtiani, Luke J. Whitesell, Shamil Sunyaev, Bonnie Berger, Albert-Laszlo Barabasi, Benoit Charloteaux, David E. Hill, Tong Hao, Frederick P. Roth, Yu Xia, Albertha J. M. Walhout, Susan Lindquist, Marc Vidal
Review
Clinical Neurology
Vikram Khurana, Daniel E. Tardiff, Chee Yeun Chung, Susan Lindquist
NATURE REVIEWS NEUROLOGY
(2015)
Article
Clinical Neurology
Ganqiang Liu, Joseph J. Locascio, Jean-Christophe Corvol, Brendon Boot, Zhixiang Liao, Kara Page, Daly Franco, Kyle Burke, Iris E. Jansen, Ana Trisini-Lipsanopoulos, Sophie Winder-Rhodes, Caroline M. Tanner, Anthony E. Lang, Shirley Eberly, Alexis Elbaz, Alexis Brice, Graziella Mangone, Bernard Ravina, Ira Shoulson, Florence Cormier-Dequaire, Peter Heutink, Jacobus J. van Hilten, Roger A. Barker, Caroline H. Williams-Gray, Johan Marinus, Clemens R. Scherzer
Review
Clinical Neurology
Ryan R. Walsh, Florian Krismer, Wendy R. Galpern, Gregor K. Wenning, Phillip A. Low, Glenda Halliday, Walter J. Koroshetz, Janice Holton, Niall P. Quinn, Olivier Rascol, Leslie M. Shaw, David Eidelberg, Pam Bower, Jeffrey L. Cummings, Victor Abler, Judy Biedenharn, Gal Bitan, David J. Brooks, Patrik Brundin, Hubert Fernandez, Philip Fortier, Roy Freeman, Thomas Gasser, Art Hewitt, Guenter U. Hoeglinger, Matt J. Huentelman, Poul H. Jensen, Andreas Jeromin, Un Jung Kang, Horacio Kaufmann, Lawrence Kellerman, Vikram Khurana, Thomas Klockgether, Woojin Scott Kim, Carol Langer, Peter LeWitt, Eliezer Masliah, Wassilios Meissner, Ronald Melki, Susanne Ostrowitzki, Steven Piantadosi, Werner Poewe, David Robertson, Cyndi Roemer, Dale Schenk, Michael Schlossmacher, Jeremy D. Schmahmann, Klaus Seppi, Lily Shih, Andrew Siderowf, Glenn T. Stebbins, Nadia Stefanova, Shoji Tsuji, Sharon Sutton, Jing Zhang
Article
Multidisciplinary Sciences
Shuchi Mittal, Kjetil Bjornevik, Doo Soon Im, Adrian Flierl, Xianjun Dong, Joseph J. Locascio, Kristine M. Abo, Elizabeth Long, Ming Jin, Bing Xu, Yang K. Xiang, Jean-Christophe Rochet, Anders Engeland, Patrizia Rizzu, Peter Heutink, Tim Bartels, Dennis J. Selkoe, Barbara J. Caldarone, Marcie A. Glicksman, Vikram Khurana, Birgitt Schule, David S. Park, Trond Riise, Clemens R. Scherzer
Article
Biochemistry & Molecular Biology
Chee Yeun Chung, Vikram Khurana, Song Yi, Nidhi Sahni, Ken H. Loh, Pavan K. Auluck, Valeriya Baru, Namrata D. Udeshi, Yelena Freyzon, Steven A. Carr, David E. Hill, Marc Vidal, Alice Y. Ting, Susan Lindquist
Article
Biochemistry & Molecular Biology
Vikram Khurana, Jian Peng, Chee Yeun Chung, Pavan K. Auluck, Saranna Fanning, Daniel F. Tardiff, Theresa Bartels, Martina Koeva, Stephen W. Eichhorn, Hadar Benyamini, Yali Lou, Andy Nutter-Upham, Valeriya Baru, Yelena Freyzon, Nurcan Tuncbag, Michael Costanzo, Bryan-Joseph San Luis, David C. Schoendorf, M. Inmaculada Barrasa, Sepehr Ehsani, Neville Sanjana, Quan Zhong, Thomas Gasser, David P. Bartel, Marc Vidal, Michela Deleidi, Charles Boone, Ernest Fraenkel, Bonnie Berger, Susan Lindquist
Article
Clinical Neurology
Hongliu Ding, Kaltra Dhima, Kaitlin C. Lockhart, Joseph J. Locascio, Ashley N. Hoesing, Karen Duong, Ana Trisini-Lipsanopoulos, Michael T. Hayes, U. Shivraj Sohur, Anne-Marie Wills, Brit Mollenhauer, Alice W. Flaherty, Albert Y. Hung, Nicte Mejia, Vikram Khurana, Stephen N. Gomperts, Dennis J. Selkoe, Michael A. Schwarzschild, Michael G. Schlossmacher, Bradley T. Hyman, Lewis R. Sudarsky, John H. Growdon, Clemens R. Scherzer
Article
Multidisciplinary Sciences
Chee Yeun Chung, Vikram Khurana, Pavan K. Auluck, Daniel F. Tardiff, Joseph R. Mazzulli, Frank Soldner, Valeriya Baru, Yali Lou, Yelena Freyzon, Sukhee Cho, Alison E. Mungenast, Julien Muffat, Maisam Mitalipova, Michael D. Pluth, Nathan T. Jui, Birgitt Schuele, Stephen J. Lippard, Li-Huei Tsai, Dimitri Krainc, Stephen L. Buchwald, Rudolf Jaenisch, Susan Lindquist
Article
Multidisciplinary Sciences
Daniel F. Tardiff, Nathan T. Jui, Vikram Khurana, Mitali A. Tambe, Michelle L. Thompson, Chee Yeun Chung, Hari B. Kamadurai, Hyoung Tae Kim, Alex K. Lancaster, Kim A. Caldwell, Guy A. Caldwell, Jean-Christophe Rochet, Stephen L. Buchwald, Susan Lindquist
Article
Cell Biology
Benjamin M. Vincent, Daniel F. Tardiff, Jeff S. Piotrowski, Rebecca Aron, Matthew C. Lucas, Chee Yeun Chung, Helene Bacherman, YiQun Chen, Michelle Pires, Radha Subramaniam, Dimple B. Doshi, Heather Sadlish, Waseem K. Raja, Eric J. Solis, Vikram Khurana, Bertrand Le Bourdonnec, Robert H. Scannevin, Kenneth J. Rhodes
Article
Cell Biology
Isabel Lam, Erinc Hallacli, Vikram Khurana
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2020)
Article
Clinical Neurology
Mar Carmona-Abellan, Inigo Gabilondo, Ane Murueta-Goyena, Vikram Khurana, Beatriz Tijero, Maria Rosario Luquin, Marian Acera, Rock Del Pino, Jesus Gardeazabal, Ivan Martinez-Valbuena, Rosario Sanchez-Pernaute, Juan Carlos Gomez-Esteban
PARKINSONISM & RELATED DISORDERS
(2019)
Review
Biochemistry & Molecular Biology
Daniel F. Jarosz, Vikram Khurana