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
Asad Jan, Nadia Pereira Goncalves, Christian Bjerggaard Vaegter, Poul Henning Jensen, Nelson Ferreira
Summary: The pathological aggregation of presynaptic protein alpha-synuclein and its propagation through synaptically coupled neuroanatomical tracts are believed to underlie the progression of Parkinson's disease and other synucleinopathies. Understanding the mechanisms of alpha-synuclein propagation may provide insights into the etiology of PD and identify new therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Tapan Behl, Sachin Kumar, Ziyad M. Althafar, Aayush Sehgal, Sukhbir Singh, Neelam Sharma, Vishnu Nayak Badavath, Shivam Yadav, Saurabh Bhatia, Ahmed Al-Harrasi, Yosif Almoshari, Mohannad A. Almikhlafi, Simona Bungau
Summary: In the past decade, researchers have found that seemingly unrelated neurodegenerative disorders, such as Parkinson's disease, share remarkable cellular and molecular biology similarities. Protein misfolding and aggregation play a role in all of these diseases, leading to the formation of inclusion bodies in cells. The discovery of disease-causing gene alterations related to the ubiquitin-proteasome pathway proteins in Parkinson's disease has strengthened the connection between this pathway and neurodegeneration. However, the specific molecular linkages between these systems and the pathogenesis of these diseases are still unknown and controversial.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tae-In Kam, Hyejin Park, Shih-Ching Chou, Jonathan G. Van Vranken, Melanie J. Mittenbuhler, Hyeonwoo Kim, A. Mu, Yu Ree Choi, Devanik Biswas, Justin Wang, Yu Shin, Alexis Loder, Senthilkumar S. Karuppagounder, Christiane D. Wrann, Valina L. Dawson, Bruce M. Spiegelman, Ted M. Dawson
Summary: This study shows that irisin can prevent neurodegeneration caused by pathological alpha-synuclein in Parkinson's disease, and it also reduces motor deficits. Irisin functions by enhancing endolysosomal degradation of pathologic alpha-synuclein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Ritu Soni, Prashant Delvadia, Amit Joharapurkar, Jigna Shah
Summary: Parkinson's disease (PD) is a common progressive disorder characterized by deposition of inclusion bodies on dopaminergic neurons in the brain. The major component of these inclusion bodies is α-synuclein aggregates, which gradually propagate PD pathology. Underexplored molecular targets could potentially aid in the development of novel therapeutics for PD.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Analytical
Yu P. Zhang, Evgeniia Lobanova, Derya Emin, Sergey V. Lobanov, Antonina Kouli, Caroline H. Williams-Gray, David Klenerman
Summary: This study introduces a new method for the diagnosis of early Parkinson's disease. The results show that the proportion of soluble alpha-synuclein aggregates can distinguish between Parkinson's disease patients and control groups, with Parkinson's disease patients having a higher proportion of larger and rounder alpha-synuclein aggregates. By combining the number and morphology of the aggregates, a new biomarker with improved accuracy for early Parkinson's disease diagnosis was constructed.
ANALYTICAL CHEMISTRY
(2023)
Article
Neurosciences
Jun Zhao, Buyan Pan, Marie Fina, Yun Huang, Marie Shimogawa, Kelvin C. Luk, Elizabeth Rhoades, E. James Petersson, Dawei W. Dong, Anna Kashina
Summary: In this study, the arginylation of alpha-synuclein (alpha-syn) was found to occur at two sites, E46 and E83, in human brain tissue. The level of arginylation was inversely correlated with overall alpha-syn levels and patient age, suggesting a potential neuroprotective role of alpha-syn arginylation in preventing abnormal accumulation during neurodegeneration and aging in the human brain.
TRANSLATIONAL NEURODEGENERATION
(2022)
Review
Biochemistry & Molecular Biology
Natasha S. R. Bidesi, Ida Vang Andersen, Albert D. Windhorst, Vladimir Shalgunov, Matthias M. Herth
Summary: Parkinson's disease is a widespread neurodegenerative disorder characterized by alpha-synuclein accumulation and dopaminergic neurons loss. Molecular imaging techniques such as MRI, SPECT, and PET have shown effectiveness in aiding clinical diagnosis and understanding the heterogeneity of PD. However, challenges remain in using molecular imaging for early diagnosis and differentiation from atypical parkinsonisms.ongoing research focuses on new imaging targets, particularly alpha-synuclein, for detecting pathological changes related to PD.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Clinical Neurology
Manuel Flores-Leon, Tiago Fleming Outeiro
Summary: The accumulation of proteinaceous inclusions in the brain is a common feature among neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Lipid biology has been implicated as important drivers of PD, playing a role in aSyn accumulation and spreading, mitochondrial dysfunction, and ER stress. It suggests that PD should not only be seen as a proteinopathy but also as a lipidopathy.
ACTA NEUROPATHOLOGICA
(2023)
Article
Neurosciences
Xin Yuan, Yingxu Yang, Danhao Xia, Lanxia Meng, Mingyang He, Chaoyang Liu, Zhentao Zhang
Summary: This study demonstrates that SiO2 NPs have significant effects on inducing PD-like pathology, including promoting phosphorylation and aggregation of alpha-synuclein, impairing mitochondria, causing oxidative stress, disrupting autophagy function, and leading to neuronal apoptosis.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
A. Anandhan, W. Chen, N. Nguyen, L. Madhavan, M. Dodson, D. D. Zhang
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the accumulation of alpha-synuclein and its negative effects on neuronal function and viability. This study demonstrates that loss of NRF2, a critical anti-ferroptotic mediator, increases markers of ferroptosis in PD-relevant brain regions. The increased ferroptosis is associated with age and genotype-dependent increase in alpha-syn pathology and behavioral deficits. The findings suggest targeting the vicious cycle of alpha-syn overexpression and NRF2 suppression as a potential means of preventing PD onset and progression.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Clinical Neurology
Etienne C. Hirsch, David G. Standaert
Summary: Parkinson's disease is a progressive and debilitating disorder with neuroinflammation playing a role in its pathophysiology. Research into the neuroinflammatory processes of Parkinson's disease is ongoing, with many unanswered questions still remaining to be explored for the development of effective treatments.
MOVEMENT DISORDERS
(2021)
Review
Biochemistry & Molecular Biology
Jennifer Murphy, Declan P. McKernan
Summary: This systematic review investigates the role of aggregated alpha-synuclein on synaptic and axonal proteins in Parkinson's disease models. The review provides evidence that aggregated alpha-synuclein can lead to dysregulation or redistribution of synaptic and axonal proteins. However, due to the high quantity of variables used in the research investigations, it is challenging to determine the exact effect of alpha-synuclein on protein expression. Thus, a more standardized experimental approach is crucial for future studies.
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
Multidisciplinary Sciences
Shiqing Zhang, Jiang Xie, Ying Xia, Shu Yu, Zhili Gu, Ruili Feng, Guanghong Luo, Dong Wang, Kai Wang, Meng Jiang, Xiao Cheng, Hai Huang, Wu Zhang, Tieqiao Wen
SCIENTIFIC REPORTS
(2015)
Article
Multidisciplinary Sciences
Yuqiong Xie, Qiang Li, Qingbo Yang, Mei Yang, Zhifeng Zhang, Liucun Zhu, Huang Yan, Ruili Feng, Shiqing Zhang, Chen Huang, Zengrong Liu, Tieqiao Wen
SCIENTIFIC REPORTS
(2014)
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)
