Review
Neurosciences
Iryna Kamienieva, Jerzy Duszynski, Joanna Szczepanowska
Summary: The familial form of Parkinson's disease is linked to mutations in specific genes, with mutations in the parkin gene being one of the most common causes of early-onset PD. Mitochondrial dysfunction is an emerging active player in the pathology of neurodegenerative diseases, as mitochondria are highly dynamic structures integrated with many cellular functions.
TRANSLATIONAL NEURODEGENERATION
(2021)
Article
Biochemistry & Molecular Biology
Iryna Kamienieva, Agata Charzynska, Jerzy Duszynski, Dominika Malinska, Joanna Szczepanowska
Summary: Most cases of Parkinson's disease are idiopathic and their causes are unknown. However, a small percentage of cases are caused by genetic mutations, with the parkin gene mutation being the most common. Mitochondrial dysfunction is believed to play a role in both idiopathic and genetic Parkinson's disease. However, different studies have reported inconsistent data on mitochondrial changes, which may be due to the genetic variability of the disease. This study investigates the mitochondrial function and dynamics in fibroblasts from Parkinson's disease patients with parkin mutations. Cluster analysis of the data revealed characteristic features of Parkinson's disease fibroblasts, including smaller and less complex mitochondrial networks, as well as decreased levels of mitochondrial biogenesis regulators and mitophagy mediators.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Immunology
Qi Peng, Dong Luo, Yi Yang, Yinghua Zhu, Qingming Luo, Huan Chen, Dapeng Chen, Zhongjun Zhou, Xiaomei Lu
Summary: This study reports a case of APLAID syndrome with a novel PLCG2 mutation, and the patient's immune phenotype and genotype were altered. This study is of great significance for the expansion of APLAID-associated immune phenotype and genotype.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Chang Liu, Weifeng Yuan, Hao Yang, Junqing Ni, Linke Tang, Heci Zhao, Donna Neumann, Xiuyan Ding, Liqian Zhu
Summary: Phospholipase C gamma 1 (PLC-gamma 1) plays an important role in the replication process of bovine herpesvirus 1 (BoHV-1), specifically in the Golgi apparatus.
MICROBIOLOGY SPECTRUM
(2023)
Review
Biochemistry & Molecular Biology
Chi-Jing Choong, Hideki Mochizuki, Cesar Borlongan
Summary: Mitochondrial dysregulation is strongly associated with the pathogenesis of Parkinson's disease (PD), with mutated genes affecting mitochondrial features. Disruption of mitochondrial quality control and abnormal secretion of mitochondrial contents play a role in PD, and circulating mitochondrial DNAs can elicit inflammatory response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Esha Sircar, Sristi Raj Rai, Mark A. Wilson, Michael G. Schlossmacher, Rajib Sengupta
Summary: Parkinson's disease is a rapidly growing neurodegenerative disorder with a strong genetic component. Aberrant S-nitrosylation of proteins like Parkin, DJ-1, and PINK1 may contribute to the pathogenesis of PD, emphasizing the importance of this post-translational modification in neuronal health.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Biochemistry & Molecular Biology
Tohru Kitada, Mustafa T. Ardah, M. Emdadul Haque
Summary: Parkin, discovered 25 years ago as the gene responsible for hereditary Parkinson's disease, remains a subject of intense research interest. Despite extensive efforts, the function and mechanism of the Parkin protein in neuronal cell death and pathogenesis remain unknown. This review highlights the chronological research on the parkin gene and discusses unresolved issues, new trends in research, and the relationship between parkin and tumorigenesis from the perspective of Parkin's redox molecule.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Chang Liu, Weifeng Yuan, Hao Yang, Junqing Ni, Linke Tang, Heci Zhao, Donna Neumann, Xiuyan Ding, Liqian Zhu
Summary: During productive infection of bovine herpesvirus 1 (BoHV-1), activated form of phospholipase C gamma 1 (PLC-gamma 1), p-PLC-gamma 1(S1248), is partially located in the Golgi apparatus and associated with the viral protein gD. This phosphorylated PLC-gamma 1(S1248) may function as an escort during the trafficking of progeny virions from the Golgi apparatus to the plasma membrane.
MICROBIOLOGY SPECTRUM
(2023)
Article
Neurosciences
Zhongting Zhao, Zheng Li, Fangning Du, Yixin Wang, Yue Wu, Kah-leong Lim, Lin Li, Naidi Yang, Changmin Yu, Chengwu Zhang
Summary: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Misfolding, aggregation, and abnormal degradation of proteins are believed to be key factors in the pathogenesis of PD. Heat shock protein 70 (Hsp70) and Parkin, an E3 ubiquitin ligase, have been found to play important roles in PD pathogenesis. This review focuses on the dysregulation of Hsp70 and Parkin, their interaction, and their potential therapeutic applications in PD.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Alexander V. Blagov, Andrey G. Goncharov, Olga O. Babich, Viktoriya V. Larina, Alexander N. Orekhov, Alexandra A. Melnichenko
Summary: This review discusses the use of mitophagy activators as a class of drug compounds for the treatment of Parkinson's disease, and explores the impact of mutations in Pink1 and Parkin enzymes on mitophagy.
Article
Biochemistry & Molecular Biology
Camilla Isgro, Ludovica Spagnuolo, Elisa Pannucci, Luigi Mondello, Luca Santi, Laura Dugo, Anna Maria Sardanelli
Summary: Sumac extract from Rhus coriaria L. may have the potential to improve Parkinson's disease by modulating mitochondrial functionality to reduce H2O2 levels and increase ATP levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Collin M. Bantle, Warren D. Hirst, Andreas Weihofen, Evgeny Shlevkov
Summary: Mitochondrial dysfunction is a key feature of Parkinson's disease, impacting the functions of astrocytes in the brain. Important astrocytic functions rely on healthy mitochondria, presenting new challenges for therapeutic development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Yi-Min Sun, Hui-Ling Yu, Xin-Yue Zhou, Wei-Xi Xiong, Su-Shan Luo, Chen Chen, Feng-Tao Liu, Jue Zhao, Yi-Lin Tang, Xiao-Niu Liang, Yu-Jie Yang, Bo Shen, Yan Shen, Wen-Bo Yu, Zheng-Tong Ding, Yu An, Jian-Jun Wu, Jian Wang
Summary: The study found that patients with Parkin-EOPD showed a slower deterioration of motor symptoms and better spatial processing ability compared to genetically undefined EOPD patients. Subtyping based on genetic features may help predict Parkinson's disease progression.
MOVEMENT DISORDERS
(2021)
Review
Immunology
Na Wu, Bingqing Zhang, Tao Wang, Min Shen, Xuejun Zeng
Summary: APLAID is a rare autoinflammatory disease caused by mutations in the PLCG2 gene. This study reported a case of APLAID patient with gangrenous pyoderma and high IgE levels, carrying a novel PLCG2 mutation, which expanded the clinical phenotype and genotype of APLAID.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Neurosciences
Shenglan Hu, Jieqiong Tan, Lixia Qin, Lingling Lv, Weiqian Yan, Hainan Zhang, BeiSha Tang, Chunyu Wang
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the progressive death of dopamine neurons, with mutations in PD-related genes playing a role in neuronal pathogenesis. Molecular chaperones/co-chaperones interact with PD-related proteins to modulate their function and potentially provide new therapeutic targets for the disease progression.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Alice Filippini, Veronica Mutti, Gaia Faustini, Francesca Longhena, Ileana Ramazzina, Federica Rizzi, Alice Kaganovich, Dorien A. Roosen, Natalie Landeck, Megan Duffy, Isabella Tessari, Federica Bono, Chiara Fiorentini, Elisa Greggio, Luigi Bubacco, Arianna Bellucci, Mariacristina Missale, Mark R. Cookson, Massimo Gennarelli, Isabella Russo
Summary: The progressive neuropathological damage in Parkinson's disease is believed to be related to the spread of aggregated forms of alpha-synuclein. Clearance of extracellular alpha-synuclein by neurons may be a key mechanism to control its concentration. Clusterin, a glycoprotein associated with Alzheimer's disease, interacts with alpha-synuclein aggregates and limits their uptake by astrocytes, which may contribute to the spreading of Parkinson's pathology.
Article
Multidisciplinary Sciences
Sara Saez-Atienzar, Sara Bandres-Ciga, Rebekah G. Langston, Jonggeol J. Kim, Shing Wan Choi, Regina H. Reynolds, Yevgeniya Abramzon, Ramita Dewan, Sarah Ahmed, John E. Landers, Ruth Chia, Mina Ryten, Mark R. Cookson, Michael A. Nalls, Adriano Chio, Bryan J. Traynor
Summary: Despite progress in genetic research on ALS, the molecular mechanisms of the disease remain not fully understood. A study involving genome-wide data and polygenic risk score approach identified key biological pathways and cell types related to ALS, revealing themes like neuron projection morphogenesis and signal transduction. The findings suggest that genetic risk in ALS is consistently linked to certain types of neurons and oligodendrocytes, and certain genes may play a role in the disease. The study concludes that diverse genetic causes of ALS converge on a smaller number of common pathways and cell types.
Article
Neurosciences
Rose B. Creed, Rosalinda C. Roberts, Charlene B. Farmer, Lori L. McMahon, Matthew S. Goldberg
Summary: Loss-of-function PTEN Induced Kinase1 (PINK1) mutations lead to early-onset familial Parkinson's disease (PD) with similar characteristics to idiopathic PD. Knockout of Pink1 in rats leads to increased excitability of presynaptic neurons, altered glutamate release probability, and abnormal synaptic vesicle pool recovery, potentially contributing to striatal circuit dysfunction in PD.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Melissa Conti Mazza, Victoria Nguyen, Alexandra Beilina, Ema Karakoleva, Michael Coyle, Jinhui Ding, Christopher Bishop, Mark R. Cookson
Summary: By studying a double knockout mouse model, it was found that the deletion of both LRRK2 and RAB29 resulted in differences in behavior and PD-like pathology with aging, suggesting that targeting this pathway may be safe for therapeutic purposes in humans.
JOURNAL OF PARKINSONS DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Luis Bonet-Ponce, Mark R. Cookson
Summary: Protein coding mutations in LRRK2 cause familial Parkinson's disease, while noncoding variations increase the risk of sporadic PD. These mutations increase LRRK2 kinase activity, influencing intracellular membrane trafficking.
Article
Neurosciences
Adeel A. Memon, Micah E. Bagley, Rose B. Creed, Amy W. Amara, Matthew S. Goldberg, Lori L. McMahon
Summary: This study found no differences in basal synaptic transmission at CA3-CA1 excitatory synapses in 4-to 5-month old PINK1 knockout rats, suggesting that loss of PINK1 protein does not cause a general dysfunction of excitatory transmission throughout the brain at this young adult age when excitatory transmission is abnormal in the striatum.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Clinical Neurology
V Alanko, C. Udeh-Momoh, M. Kivipelto, A. Sandebring-Matton
Summary: Modifying lifestyle can prevent and improve Alzheimer's disease and cognitive impairment. Implementing different types of lifestyle interventions on animal models can improve cognitive abilities, alleviate pathology and inflammation, restore mitochondrial function, and have a positive impact on neurogenesis and cell survival. Although some important pathways have been identified, further research is needed to confirm these mechanisms of action.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Julen Goikolea, Gorka Gerenu, Makrina Daniilidou, Francesca Mangialasche, Patrizia Mecocci, Tiia Ngandu, Juha Rinne, Alina Solomon, Miia Kivipelto, Angel Cedazo-Minguez, Anna Sandebring-Matton, Silvia Maioli
Summary: This study found that serum Trx80 levels are associated with AD disease stage and risk factors such as age and ApoE4 genotype. This suggests that Trx80 could have potential as a serum biomarker for AD.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Neurosciences
Rose B. Creed, Adeel A. Memon, Sindhu P. Komaragiri, Sandeep K. Barodia, Matthew S. Goldberg
Summary: The study suggests that intrastriatal injection of mice with small length PFFs induces extensive bilateral protein aggregates, significant unilateral nigral cell loss, and altered levels of mitochondrial proteins and respiratory chain activity, offering insights into the role of mitochondrial dysfunction in alpha-synucleinopathies and potential for testing neuroprotective therapies.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Anna Rosenberg, Ulf Ohlund-Wistbacka, Anette Hall, Alexandre Bonnard, Goran Hagman, Marie Ryden, Charlotta Thunborg, Fleur Wiggenraad, Anna Sandebring-Matton, Alina Solomon, Miia Kivipelto
Summary: This study conducted in a memory clinic in Sweden applied the ATN system to assess patient eligibility for anti-amyloid treatment, showing that the majority of patients did not meet the criteria and emphasizing the need for continued development of disease-modifying treatments with different mechanisms.
Article
Clinical Neurology
Patrick Oeckl, Marina Bluma, Marco Bucci, Steffen Halbgebauer, Konstantinos Chiotis, Anna Sandebring-Matton, Nicholas J. Ashton, Guglielmo Di Molfetta, Lana Grotschel, Miia Kivipelto, Kaj Blennow, Henrik Zetterberg, Irina Savitcheva, Agneta Nordberg, Markus Otto
Summary: Plasma beta-synuclein levels were found to be higher in individuals with Alzheimer's disease and mild cognitive impairment with amyloid-beta positivity. It demonstrated good discrimination and prediction of amyloid-beta status. The correlation between plasma beta-synuclein and amyloid-beta PET was observed in multiple cortical regions. These findings suggest that beta-synuclein is not a direct marker of amyloid-beta pathology and highlight the different longitudinal dynamics of synaptic degeneration and amyloid deposition in Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Vilma Alanko, Adhara Gaminde-Blasco, Tania Quintela-Lopez, Raul Loera-Valencia, Alina Solomon, Ingemar Bjorkhem, Angel Cedazo-Minguez, Silvia Maioli, Graziella Tabacaru, Maria Latorre-Leal, Carlos Matute, Miia Kivipelto, Elena Alberdi, Anna Sandebring-Matton
Summary: Oxidized cholesterol metabolite 27-hydroxycholesterol (27-OH) is a potential link between hypercholesterolemia and neurodegenerative diseases as it can cross the blood-brain barrier. This study found that high levels of 27-OH can impact oligodendrocyte function and contribute to the disconnection of neural networks in neurodegenerative diseases.
Article
Clinical Neurology
C. Udeh-Momoh, B. Zheng, A. Sandebring-Matton, G. Novak, M. Kivipelto, L. Jonsson, L. Middleton
Summary: This study validated the capacity of plasma A beta 42/A beta 40 measured using six different assays to predict amyloid positivity in cognitively unimpaired participants and discriminating between cognitively unimpaired and Alzheimer's disease cases. The use of ultrasensitive immunoassays and high-performance immunoprecipitation coupled with mass spectrometry for measurement of plasma A beta 42/A beta 40 showed diagnostic value in detecting PET amyloid positivity, with potential clinical utility in AD prevention trials and clinical care.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)