Article
Biology
Harry S. Xenias, Chuyu Chen, Shuo Kang, Suraj Cherian, Xiaolei Situ, Bharanidharan Shanmugasundaram, Guoxiang Liu, Giuseppe Scesa, C. Savio Chan, Loukia Parisiadou
Summary: Studies of mouse models with different mutations of the LRRK2 gene associated with Parkinson's disease reveal distinct alterations at multiple levels, including electrochemical, electrophysiological, molecular, and behavioral. The findings suggest that LRRK2 mutations affect striatal function, but the specific changes vary between different mutations. The results provide mechanistic insights for developing treatment strategies for Parkinson's disease patients.
COMMUNICATIONS BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Maria Dolores Perez-Carrion, Inmaculada Posadas, Javier Solera, Valentin Cena
Summary: This review summarizes the main pathological mutations in LRRK2 that contribute to Parkinson's disease and discusses the different cellular and therapeutic strategies to correct LRRK2 homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Yangshin Park, Jingling Liao, Quyen Q. Hoang
Summary: This review discusses new insights gained from recent cryo-EM structures of LRRK2, aiming to understand its mechanisms of action and explore potential new therapeutic avenues.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ranjan K. Singh, Ahmed Soliman, Giambattista Guaitoli, Eliza Stoermer, Felix von Zweydorf, Thomas Dal Maso, Asmaa Oun, Laura Van Rillaer, Sven H. Schmidt, Deep Chatterjee, Joshua A. David, Els Pardon, Thomas U. Schwartz, Stefan Knapp, Eileen J. Kennedy, Jan Steyaert, Friedrich W. Herberg, Arjan Kortholt, Christian Johannes Gloeckner, Wim Versees
Summary: Mutations in the LRRK2 gene are a leading cause of Parkinson's disease, while overactivation of LRRK2 is associated with idiopathic form of the disease. Researchers have identified and characterized nanobodies that can bind to different domains of LRRK2 and inhibit or activate its activity. These nanobodies act through an allosteric inhibitor mechanism and provide potential therapeutic strategies for Parkinson's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Jasmin Galper, Woojin S. Kim, Nicolas Dzamko
Summary: Genetic alterations in the LRRK2 gene are a common risk factor for Parkinson's disease. LRRK2 alterations are associated with changes in lipid pathways, which can lead to cellular pathology.
Review
Medicine, General & Internal
Xiao-Yan Yao, Li-Na Guan, Qi Chen, Chao Ren
Summary: The pathogenesis of Parkinson's disease involves multiple factors such as heredity, environment, and ageing. Mutations in LRRK2 are recognized as risk factors and play a significant role in the degeneration of dopaminergic neurons in PD. Glial hyperactivation-mediated neuroinflammation is also involved in the development of PD.
POSTGRADUATE MEDICAL JOURNAL
(2023)
Article
Cell Biology
Sara R. Oliveira, Pedro A. Dionisio, Maria M. Gaspar, Leonor Correia Guedes, Miguel Coelho, Mario M. Rosa, Joaquim J. Ferreira, Joana D. Amaral, Cecilia M. P. Rodrigues
Summary: The study reveals a protective role of miR-335 in experimental models of Parkinson's disease, showing its ability to combat inflammation and neurodegenerative events.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Dominika Natalia Wojewska, Arjan Kortholt
Summary: This review provides a comprehensive overview of the current state of the art, presenting recent developments and challenges in developing LRRK2 inhibitors, and discussing extensively the potential targeting strategies from the protein perspective. As currently there are three LRRK2-targeting agents in clinical trials, more developments are predicted in the upcoming years.
Review
Biochemistry & Molecular Biology
Ailyn Irvita Ravinther, Hemaniswarri Dewi Dewadas, Shi Ruo Tong, Chai Nien Foo, Yu-En Lin, Cheng-Ting Chien, Yang Mooi Lim
Summary: Parkinson's disease is a common neurodegenerative disease affecting the ageing population, and its prevalence has increased in recent years. Mutations in Leucine-rich-repeat-kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease, and aberrant LRRK2 kinase activity is also associated with idiopathic Parkinson's disease. This review aims to categorize and synthesize current information on LRRK2-linked Parkinson's disease and identify potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ahsan Usmani, Farbod Shavarebi, Annie Hiniker
Summary: Point mutations in LRRK2 are common causes of familial and apparent sporadic Parkinson's disease. LRRK2-driven PD is clinically indistinguishable from sporadic PD, making it a valuable genetic model. Recent research highlights LRRK2's functions in the endolysosomal system and regulation by Rab GTPases, as well as its interaction with the cytoskeleton for protein degradation and inhibitor therapies. Interactions between LRRK2 and other PD-driving genes may illuminate broader cellular pathways disrupted in PD.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
News Item
Biochemistry & Molecular Biology
Surya K. De
Summary: This patent describes the use of novel pyrroloppyrimidine compounds as LRRK2 kinase inhibitors for the treatment or prevention of diseases associated with LRRK2 kinase activity, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS).
CURRENT MEDICINAL CHEMISTRY
(2023)
Review
Environmental Sciences
Sachin Kumar, Tapan Behl, Aayush Sehgal, Sridevi Chigurupati, Sukhbir Singh, Vasudevan Mani, Maha Aldubayan, Ahmed Alhowail, Satvinder Kaur, Saurabh Bhatia, Ahmed Al-Harrasi, Vetriselvan Subramaniyan, Shivkanya Fuloria, Neeraj Kumar Fuloria, Mahendran Sekar, Mohamed M. Abdel Daim
Summary: Major breakthroughs in understanding the role of biology in Parkinson's disease (PD) have identified mitochondrial dysfunction and the enzyme leucine-rich repeat kinase 2 (LRRK2) as important factors in the pathogenesis of the disease. Inhibiting LRRK2 kinase activity shows promise in preventing endolysosomal dysfunction and neurodegeneration in PD, making LRRK2 inhibitors potentially useful therapeutic targets.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Suzanne R. Pfeffer
Summary: Rab GTPases are critical regulators of secretory and endocytic pathways. Mutations in LRRK2 kinase lead to Parkinson's disease, and Rab GTPases are important substrates of LRRK2. Phosphorylation of Rab proteins by LRRK2 influences effector selection and has significant consequences for cell pathophysiology.
Article
Biochemistry & Molecular Biology
Jun Ogata, Kentaro Hirao, Kenya Nishioka, Arisa Hayashida, Yuanzhe Li, Hiroyo Yoshino, Soichiro Shimizu, Nobutaka Hattori, Yuzuru Imai
Summary: A novel LRRK2 variant-p.G2294R located in the WD40 domain was detected in a patient with familial Parkinson's disease through targeted gene-panel screening. This variant was found to be highly destabilized at the protein level. Experimental results showed upregulated expression of the LRRK2 p.G2294R protein in the patient's peripheral blood lymphocytes, while macrophages differentiated from the same blood sample exhibited decreased levels of LRRK2 protein. Additionally, reduced phagocytic activity was observed in pathogenic yeasts and alpha-synuclein fibrils.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chen Dong, Chandrashekhar Honrao, Leonardo O. Rodrigues, Josephine Wolf, Keri B. Sheehan, Matthew Surface, Roy N. Alcalay, Elizabeth M. O'Day
Summary: Parkinson's disease is a progressive neurodegenerative disease with motor and nonmotor function loss. This study identified metabolic markers of PD in plasma and developed a machine learning model for PD diagnosis with high accuracy. The findings provide insights for the development of diagnostic tools for PD.
Letter
Clinical Neurology
Seyed Amir Hassan Habibi, Gholamali Shahidi, Mansour Parvaresh, Alfonso Fasano, Maryam Pouranian, Narges Yazdi, Farhad Modara, Maryam Mehdizadeh, Ghorban Taghizadeh, Mohammad Rohani
NEUROLOGICAL SCIENCES
(2020)
Article
Microbiology
Seyed A. Ghorashi, Jane Heller, Quincy Zhang, Shafi Sahibzada
JOURNAL OF CLINICAL MICROBIOLOGY
(2020)
Article
Veterinary Sciences
Shubhagata Das, Kate Smith, Subir Sarker, Andrew Peters, Katherine Adriaanse, Paul Eden, Seyed A. Ghorashi, Jade K. Forwood, Shane R. Raidal
JOURNAL OF WILDLIFE DISEASES
(2020)
Article
Engineering, Biomedical
Ehsan Pourghayoomi, Saeed Behzadipour, Mehdi Ramezani, Mohammad Taghi Joghataei, Gholam Ali Shahidi
BIOMEDICAL ENGINEERING ONLINE
(2020)
Article
Clinical Neurology
Mohammad Hossein Abbasi, Sara Esmaeili, Seyed Amirhassan Habibi, Gholam Ali Shahidi
JOURNAL OF CLINICAL NEUROSCIENCE
(2020)
Article
Clinical Neurology
Yasaman Saeedi, Maryam Ghadimi, Mohammad Rohani, Maziar Emamikhah, Gholamali Shahidi, Mehdi Moghaddasi, Seyed Amir Hassan Habibi
Summary: This study assessed the effects of discontinuing anticholinergic medications on motor function, freezing of gait, and falling in patients with Parkinson's disease. The results demonstrated significant improvements in motor symptoms, freezing of gait, and falling incidences after discontinuation of anticholinergic drugs, emphasizing the necessity for clinicians to carefully consider the use of these medications in treatment strategies for PD patients.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2021)
Article
Clinical Neurology
Mona Ramezani Ghamsari, Shadi Ghourchian, Maziar Emamikhah, Mahdi Safdarian, Gholamali Shahidi, Mansour Parvaresh, Mehdi Moghaddasi, Seyed Amir Hassan Habibi, Renato P. Munhoz, Mohammad Rohani
Summary: The study confirms the overall success of GPi-DBS in pediatric patients with DYT1 dystonia, showing significant and long-lasting positive effects on motor and cognitive functions. Long-term follow-up revealed no prominent side effects.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2021)
Article
Clinical Neurology
Fatemeh Moghadas, Seyedamirhassan Habibi, Farhad Modara, Gholam Ali Shahidi, Giovanna Zorzi, Mehdi Moghaddasi, Tayebeh Lotfi, Maryam Mehdizadeh
CLINICAL NEUROLOGY AND NEUROSURGERY
(2021)
Article
Clinical Neurology
Dirk Dressler, Maria Concetta Altavista, Eckart Altenmueller, Roongroj Bhidayasiri, Saeed Bohlega, Pedro Chana, Tae Mo Chung, Carlo Colosimo, Klemens Fheodoroff, Pedro J. Garcia-Ruiz, Beomseok Jeon, Lingjing Jin, Petr Kanovsky, Ivan Milanov, Federico Micheli, Olga Orlova, Sanjay Pandey, Zvezdan Pirtosek, Maja Relja, Raymond Rosales, Jose Alberto Sagastegui-Rodriguez, Gholam Ali Shahidi, Sofia Timerbaeva, Xinhua Wan, Uwe Walter, Fereshte Adib Saberi
Summary: Botulinum toxin (BT) therapy is a highly individualized and complex treatment that requires treatment algorithms and injection schemes to be tailored to each patient. Consensus guidelines have been updated and improved by acknowledging recent advances in treatment algorithms and providing more detailed dosing data. Collaborating with an international panel of experts has further enhanced the guidelines for BT therapy.
JOURNAL OF NEURAL TRANSMISSION
(2021)
Review
Food Science & Technology
Madalyn Hobbs, Marefa Jahan, Seyed A. Ghorashi, Bing Wang
Summary: Human milk oligosaccharides (HMOs) are important components in breast milk with various health benefits for newborns, while most infant formulas lack these oligosaccharides. The diversity and concentration of oligosaccharides in mammalian milk vary among species, and sialylated milk oligosaccharides (SMOs) are gaining attention in research due to their beneficial nature.
Article
Multidisciplinary Sciences
Petrina Young, Pol Tarce, Sadhana Adhikary, Joanne Connolly, Tim Crawshaw, Seyed A. Ghorashi
Summary: The study successfully identified Campylobacter hepaticus as the causative agent of spotty liver disease through PCR and high-resolution melt curve analysis, providing a rapid and robust technique for genotyping different Campylobacter species.
Article
Veterinary Sciences
Mojdeh Sadat Ghorashi, Sameer Dinkar Pant, Seyed Ali Ghorashi
Summary: The accuracies of PCR and LAMP assay in detecting salmonella in poultry clinical samples were compared with bacterial culture. The LAMP assay showed high sensitivity and specificity, and can be used in the field. HRM curve analysis following PCR can differentiate salmonella isolates based on their melting points.
Article
Agriculture, Dairy & Animal Science
Brianna N. Maslen, Lesley A. Gray, Seyed A. Ghorashi, Jason D. White, Michael A. Campbell, Sameer D. Pant
Summary: Microorganisms in the gut have a significant impact on the health and productivity of livestock. When cattle are placed in feedlots, there are observable changes in the gut microorganisms, including reduced diversity within individuals and increased differences between animals.
Article
Veterinary Sciences
Charlotte Garner, Cyril Stephen, Sameer Dinkar Pant, Seyed Ali Ghorashi
Summary: In this study, a combination of Loop-Mediated Isothermal Amplification (LAMP) and PCR techniques with high-resolution melt (HRM) curve analysis were used to analyze different bacterial species and clinical samples. HRM curve analysis genotyped all clinical samples into three distinct groups based on differences in melting curve profiles, which reflected DNA variation in the sorD gene. A mathematical model based on Genetic Confidence Percentage (GCP) and a cut-off point value were established for HRM curve analysis, enabling differentiation of S. zooepidemicus isolates without visual interpretation of curve profiles. PCR-HRM and LAMP assay showed high accuracy in detecting S. zooepidemicus, with PCR-HRM having a turnaround time of six hours and LAMP assay requiring 120 minutes compared to the minimum three days for routine bacterial culture method. These rapid diagnostic tests can benefit mares suspected of endometritis by allowing early detection of S. zooepidemicus and proper treatment before breeding, reducing unnecessary treatment and antibiotic resistance.
VETERINARY RESEARCH COMMUNICATIONS
(2023)
Article
Neurosciences
Masoomeh Sabaei, Saba Rahimian, Arsh Haj Mohamad Ebrahim Ketabforoush, Homa Rasoolijazi, Babak Zamani, Fahime Hajiakhoundi, Mansoureh Soleimani, Gholamali Shahidi, Mahmood Faramarzi
Summary: This study suggests that salivary levels of p-tau, alpha-syn, and A beta 1-42 can be used as biomarkers for early diagnosis of Alzheimer's disease (AD) and Parkinson's disease (PD). The level of A beta is higher in both PD and AD patients, while the level of alpha-syn is lower. Salivary p-tau level can help differentiate between AD and PD. These investigations have the potential to reduce the use of invasive diagnostic methods and alleviate the suffering of AD and PD patients.
IBRO NEUROSCIENCE REPORTS
(2023)