Article
Chemistry, Medicinal
Sophia D. Staerz, Corey L. Jones, Jetze J. Tepe
Summary: Neurodegenerative diseases are characterized by the oligomerization and aggregation of specific intrinsically disordered proteins, and enhancing 20S proteasome-mediated proteolysis could be a promising therapeutic approach.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Sarah E. Sandler, Robert I. Horne, Sara Rocchetti, Robert Novak, Nai-Shu Hsu, Marta Castellana Cruz, Z. Faidon Brotzakis, Rebecca C. Gregory, Sean Chia, Goncalo J. L. Bernardes, Ulrich F. Keyser, Michele Vendruscolo
Summary: This study presents a single-molecule approach using solid-state nanopores and multiplexed DNA barcoding for the detection and quantification of protein oligomers. By studying alpha-synuclein oligomers and inhibitors of alpha-synuclein aggregation, the potential applicability of this method to the development of diagnostic and therapeutic methods for Parkinson's disease is demonstrated.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Mireille M. A. E. Claessens, Jonathan Vaneyck, Therese A. Yousif, Ine Segers-Nolten, Christian Blum
Summary: Amyloid fibrils of alpha-synuclein have been identified as a biomarker for Parkinson's disease. Seed amplification assays can detect the presence of these fibrils and have potential for PD diagnosis. Quantitative analysis of alpha-synuclein fibrils can provide insights into disease progression and severity.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Multidisciplinary Sciences
Jack Kelly, Rana Moyeed, Camille Carroll, Shouqing Luo, Xinzhong Li
Summary: With the aging population, it is increasingly important to understand the mechanisms of neurodegenerative diseases and identify biomarkers for early diagnosis and effective clinical trial screening. This study utilized machine learning approaches and gene expression profiling to identify blood-based biomarkers for Alzheimer's and Parkinson's disease, and explored the potential applications of deep learning methods.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Dianne K. Bryce, Chris M. Ware, Janice D. Woodhouse, Paul J. Ciaccio, J. Michael Ellis, Laxminarayan G. Hegde, Sabu Kuruvilla, Matthew L. Maddess, Carrie G. Markgraf, Karin M. Otte, Frederique M. Poulet, Lauren M. Timmins, Matthew E. Kennedy, Matthew J. Fell
Summary: Long-term treatment with LRRK2 kinase inhibitors in mice can lead to mild and reversible effects on lung histomorphology, highlighting the potential safety and tolerability of chronic LRRK2 kinase inhibition in Parkinson's disease (PD) treatment.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Oncology
Zhengcun Wu, Chengxing Xia, Chao Zhang, Delin Yang, Kaili Ma
Summary: This study investigates the role of SNCA gene in bladder cancer (BLCA) and its potential as a prognostic diagnostic biomarker. The results show that SNCA is downregulated in BLCA tumor tissues and is negatively correlated with DNA methylation. High SNCA expression is associated with poor overall survival. SNCA is also found to play a role in immune cell infiltration, particularly with T cells. Therefore, SNCA may serve as a promising prognostic biomarker in BLCA patients.
Article
Cell Biology
Dan Dou, Erin M. Smith, Chantell S. Evans, C. Alexander Boecker, Erika L. F. Holzbaur
Summary: Gain-of-function mutations in the LRRK2 gene cause Parkinson's disease by increasing phosphorylation of RAB GTPases. This disrupts the transport of autophagosomes by interfering with the coordinated regulation of cytoplasmic dynein and kinesin. The imbalance between hyperphosphorylated RABs and ARF6 induces a tug-of-war between dynein and kinesin, impairing autophagosome transport and potentially contributing to PD pathogenesis.
Article
Biochemistry & Molecular Biology
C. Alexander Boecker, Juliet Goldsmith, Dan Dou, Gregory G. Cajka, Erika L. F. Holzbaur
Summary: Mutations in the LRRK2 gene associated with Parkinson's disease lead to defects in autophagosome transport, impairing effective degradation of autophagosomal cargo in neurons.
Article
Biotechnology & Applied Microbiology
Benjamin W. Schlichtmann, Monica Hepker, Bharathi N. Palanisamy, Manohar John, Vellareddy Anantharam, Anumantha G. Kanthasamy, Balaji Narasimhan, Surya K. Mallapragada
Summary: Synucleinopathies are debilitating neurodegenerative disorders with no clinically approved therapeutic options. Multiple synergistic pathological mechanisms and misfolding of proteins contribute to disease progression, making treatment challenging. Nanocarriers can improve brain delivery of therapeutics and enable multifunctional therapies.
CURRENT OPINION IN CHEMICAL ENGINEERING
(2021)
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
Multidisciplinary Sciences
Jennifer Hope Roberts, Jian Zhang, Florent David, Amy McLean, Karen Blumenshine, Eva Mueller-Alander, Jaroslava Halper
Summary: Degenerative Suspensory Ligament Desmitis (DSLD) is a systemic disorder that affects connective tissues in horses, leading to chronic pain and lameness. Currently, DSLD can only be diagnosed through post mortem histological examination. Recent research identified potential biomarkers, BMP2 and FOS, that can be used to diagnose DSLD in living horses. Furthermore, RNA-seq analysis revealed overexpression of these genes in DSLD skin biopsies. The use of a panel containing BMP2 and FOS as diagnostic markers for DSLD in older horses is recommended.
Article
Multidisciplinary Sciences
Fubo Cheng, Wenxu Zheng, Chang Liu, Peter Antony Barbuti, Libo Yu-Taeger, Nicolas Casadei, Jeannette Huebener-Schmid, Jakob Admard, Karsten Boldt, Katrin Junger, Marius Ueffing, Henry Houlden, Manu Sharma, Rejko Kruger, Kathrin Grundmann-Hauser, Thomas Ott, Olaf Riess
Summary: Evidence suggests that increased SNCA protein is a significant risk factor for Parkinson's disease (PD). This study identifies THAP1 and CTCF as transcription regulators of SNCA in the brain. SNCA intronic enhancers show neurodevelopment-dependent activities and form enhancer clusters enriched with PD-associated single-nucleotide polymorphisms. Deletion of these enhancer clusters reduces SNCA expression in the brain by preventing the release of paused RNA polymerase II from its promoter.
Article
Cell Biology
Xudong Chen, Mingze Zhou, Sensen Zhang, Jian Yin, Ping Zhang, Xujun Xuan, Peiyi Wang, Zhiqiang Liu, Boda Zhou, Maojun Yang
Summary: The cryo-EM structures of three distinct intermediates of human ATP13A2 were reported, providing insights into the spermine transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site, and the C-terminal domain is essential for protein stability. These findings advance understanding of the polyamine transport mechanism and associated disease mutants of ATP13A2.
Article
Biochemistry & Molecular Biology
Shigeto Sato, Sachiko Noda, Satoru Torii, Taku Amo, Aya Ikeda, Manabu Funayama, Junji Yamaguchi, Takahiro Fukuda, Hiromi Kondo, Norihiro Tada, Satoko Arakawa, Masahiko Watanabe, Yasuo Uchiyama, Shigeomi Shimizu, Nobutaka Hattori
Summary: The inactivation of constitutive autophagy leads to the formation of cytoplasmic inclusions in neurons. The relationship between impaired autophagy and Lewy bodies (LBs) remains unknown. Studies have shown that p62 aggregates derived from an autophagic defect might serve as 'seeds' for LB formation, while CHCHD2 protein regulates mitochondrial morphology and p62 homeostasis by controlling the level of OPA1, impacting inclusion body formation and dopaminergic neuronal loss in an age-dependent manner.
HUMAN MOLECULAR GENETICS
(2021)
Article
Toxicology
Sierra L. Boyd, Nathan C. Kuhn, Joseph R. Patterson, Anna C. Stoll, Sydney A. Zimmerman, Mason R. Kolanowski, Joseph J. Neubecker, Kelvin C. Luk, Eric S. Ramsson, Caryl E. Sortwell, Alison Bernstein
Summary: Parkinson's disease (PD) is the fastest-growing neurological disease worldwide, suggesting a role of environmental factors. Studies have shown that persistent organic pollutants, including the organochlorine pesticide dieldrin, increase PD risk. In mice, developmental dieldrin exposure exacerbates neuronal susceptibility to MPTP and synucleinopathy.
TOXICOLOGICAL SCIENCES
(2023)