Article
Biochemistry & Molecular Biology
Gavin P. Schmitz, Manish K. Jain, Samuel T. Slocum, Bryan L. Roth
Summary: In this study, the researchers examined the effects of sequence variations in the 5-HT2AR gene on the signaling of four commonly used psychedelic drugs. They found that these genetic variations have statistically significant, but modest, effects on the efficacy and potency of the drugs. Importantly, these effects are specific to each drug.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Gavin P. Schmitz, Manish K. Jain, Samuel T. Slocum, Bryan L. Roth
Summary: Sequence variations in the 5-HT2AR gene have been found to have modest but statistically significant effects on the efficacy and potency of commonly used psychedelic drugs. The in vitro pharmacological effects of these variations are specific to each drug.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Kucwaj-Brysz, Wesam Ali, Rafal Kurczab, Sylwia Sudol-Talaj, Natalia Wilczynska-Zawal, Magdalena Jastrzebska-Wiesek, Grzegorz Satala, Barbara Mordyl, Ewa Zeslawska, Kinga Czarnota, Gniewomir Latacz, Anna Partyka, Anna Wesolowska, Wojciech Nitek, Jadwiga Handzlik, Agnieszka-Olejarz-Maciej
Summary: This research discovered highly potent dual 5-HT6/5-HT2A receptor antagonists in a group of 1,3,5-triazine compounds, which show potential in fighting Alzheimer's disease.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Johannes Morstein, Giovanna Romano, Belinda E. Hetzler, Ambrose Plante, Caleb Haake, Joshua Levitz, Dirk Trauner
Summary: This study develops tools for optical control of serotonin receptors, providing a new method for studying receptor function. By constructing a repeatable and reversible optical control system, this study lays the foundation for extending photopharmacology to the serotonin receptor family.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Christian B. M. Poulie, Eline Pottie, Icaro A. Simon, Kasper Harpsoe, Laura D'Andrea, Igor V. Komarov, David E. Gloriam, Anders A. Jensen, Christophe P. Stove, Jesper L. Kristensen
Summary: This study evaluated the biased signaling of the 5-HT2AR receptor and found that the interaction with Ser159(3x36) is crucial for signaling and efficacy. G alpha(q)-mediated signaling was more affected. These findings contribute to the development of more effective 5-HT2AR agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Orr Shahar, Alexander Botvinnik, Noam Esh-Zuntz, Michal Brownstien, Rachel Wolf, Amit Lotan, Gilly Wolf, Bernard Lerer, Tzuri Lifschytz
Summary: There is growing interest in the therapeutic potential of psilocybin. This study examined the role of different serotonergic receptors and TAAR1 in modulating the head twitch response induced by 5-HTP and psilocybin in mice. The findings suggest that compounds that modulate psychedelic-induced head twitch response may have important therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jelena Nikolic, Katarina Vukojevic, Violeta Soljic, Josip Miskovic, Martina Orlovic Vlaho, Mirna Saraga-Babic, Natalija Filipovic
Summary: We studied the expression of serotonin receptors 5-HT1A, 5-HT2A, and 5-HT3A at different stages of fetal lung development. The receptors were strongly expressed in the epithelium of the proximal airways and vascular walls during early and mid-fetal development. In the later stages, they were also expressed in type I and type II pneumocytes. The expression of 5-HT2A decreased while 5-HT3A expression increased toward the final stage of lung development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Maria Diez-Cirarda, Alberto Cabrera-Zubizarreta, Ane Murueta-Goyena, Antonio P. Strafella, Rocio Del Pino, Marian Acera, Olaia Lucas-Jimenez, Naroa Ibarretxe-Bilbao, Beatriz Tijero, Juan Carlos Gomez-Esteban, Inigo Gabilondo
Summary: Visual hallucinations (VH) are present in up to 75% of Parkinson's disease (PD) patients. However, their neural bases and participation of the visual system in VH are not well-understood in PD. This study found specific functional and structural abnormalities within the visual system in PD patients with VH, which could potentially serve as biomarkers for VH in PD.
JOURNAL OF NEUROLOGY
(2023)
Review
Neurosciences
Francisco Nieto-Escamez, Esteban Obrero-Gaitan, Irene Cortes-Perez
Summary: Non-motor symptoms in Parkinson's disease (PD) include ocular, visuoperceptive, and visuospatial impairments. Ocular impairments affect vision and eye movement, while visuoperceptive impairments involve difficulties perceiving visual stimuli accurately and visuospatial impairments affect spatial relationships and judgement. PD patients also face attention and perceptual disturbances with visual stimuli. The neurobiological bases of visual-related disorders in PD are complex and not fully understood, with changes in cortical and subcortical regions and alterations in dopamine, acetylcholine, and serotonin systems potentially involved.
Article
Clinical Neurology
Adam Fry, Dharampreet Singh, Louis Manganas, Marc L. Gordon, Christopher Christodoulou, Hoi-Chung Leung, Guy J. Schwartz
Summary: This study found a high incidence of temporal lobe epileptiform discharges in Parkinson's disease patients with visual hallucinations compared to those without. This finding suggests a possible association with a epileptogenic focus in the visual cortex and highlights the potential use of antiepileptic drugs in treatment-refractory patients, similar to Charles Bonnet syndrome, temporal lobe epilepsy, and migraine with visual aura.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Alberto Cucca, Claudia Virginia Manara, Mauro Catalan, Marco Liccari, Lucia Antonutti, Tiziana Maria Isabella Lombardo, Valentina Cenacchi, Sophie Rangan, Serena Mingolo, Carmelo Crisafulli, Franca Dore, Mauro Murgia, Tiziano Agostini, Paolo Manganotti
Summary: Visual hallucinations are common symptoms of Parkinson's Disease, and are associated with impairments in perceptual processing and modulation. This study found that perceptual performance in PD patients is related to the presence of hallucinations, as well as abnormal top-down perceptual modulation.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Health Care Sciences & Services
Sara Redensek, Tanja Blagus, Maja Trost, Vita Dolzan
Summary: Genetic variability of serotonergic genes is associated with motor complications and psychiatric adverse events caused by dopaminergic treatment in Parkinson's disease (PD), suggesting an important role of the serotonergic pathway in PD pathogenesis.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Clinical Neurology
Wei Lin Toh, Caitlin Yolland, Caroline Gurvich, James Barnes, Susan L. Rossell
Summary: This study conducted a systematic review on non-visual hallucinations in Parkinson's disease, exploring their prevalence, phenomenology, and clinical-cognitive correlates. The findings revealed that non-visual hallucinations are prevalent in Parkinson's disease and have clinical significance, highlighting the need for further research and clinical attention.
JOURNAL OF NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim, Ximena Barros-Alvarez, Ramona M. Rodriguiz, Ying Yang, Oh Sang Kweon, Tao Che, John D. McCorvy, David N. Kamber, James P. Phelan, Luan Carvalho Martins, Vladimir M. Pogorelov, Jeffrey F. DiBerto, Samuel T. Slocum, Xi-Ping Huang, Jain Manish Kumar, Michael J. Robertson, Ouliana Panova, Alpay B. Seven, Autumn Q. Wetsel, William C. Wetsel, John J. Irwin, Georgios Skiniotis, Brian K. Shoichet, Bryan L. Roth, Jonathan A. Ellman
Summary: Researchers successfully screened and synthesized molecules that can activate the 5-HT2A receptor using structure-based docking and optimization methods. These molecules exhibited potent antidepressant activity in mouse models without psychedelic effects.
Article
Neurosciences
Liangcheng Qu, Chuan Liu, Yiting Cao, Jingping Shi, Kuiying Yin, Weiguo Liu
Summary: Recent studies have found that functional connections are impaired in patients with Parkinson's disease accompanied by hallucinations even in the preclinical stage. This study investigated the impact of changes in functional connectivity between cognitive sub-regions of the cerebellum on cognitive performance in PD patients with hallucinations. Resting-state functional magnetic resonance imaging data were collected and a machine learning method was used to classify subjects based on cerebellar functional connectivity features. The results showed that FC within certain brain regions was increased in PD-H patients compared to healthy controls and PD-NH patients. These findings provide a promising and low-cost alternative for diagnosing preclinical PD-H and have implications for other degenerative brain disorders.
Article
Clinical Neurology
Kohei Fukuoka, Yasin Mamatjan, Scott Ryall, Martin Komosa, Julie Bennett, Michal Zapotocky, Julia Keith, Sten Myrehaug, Lili-Naz Hazrati, Kenneth Aldape, Normand Laperriere, Eric Bouffet, Uri Tabori, Cynthia Hawkins
Article
Clinical Neurology
R. Depoortere, T. H. Johnston, S. H. Fox, J. M. Brotchie, A. Newman-Tancredi
PARKINSONISM & RELATED DISORDERS
(2020)
Article
Neurosciences
Jay S. Schneider, Courtney A. Marshall, Lauren Keibel, Nathaniel W. Snyder, Michael P. Hill, Jonathan M. Brotchie, Tom H. Johnston, Barry D. Waterhouse, Sandhya Kortagere
Summary: Mild cognitive impairment in Parkinson's disease (PD-MCI) can manifest as deficits in various cognitive functions and may be an early symptom of the disease. Current pharmacological treatments are limited due to the involvement of multiple neurotransmitter systems. Developing therapeutics that can target both motor and cognitive impairments in PD is crucial for improving patient outcomes.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Public, Environmental & Occupational Health
Naomi P. Visanji, Piyush Madan, Alix M. B. Lacoste, Italo Buleje, Yanyan Han, Scott Spangler, Lorraine Kalia, Sharon Hensley Alford, Connie Marras
Summary: The study identified potential drugs that may reduce aSyn oligomerization through computational analysis and real-world data. Among these, the combination of ARBs and DHP-CCBs was found to be of particular interest in Parkinson's Disease.
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2021)
Article
Clinical Neurology
Nicole Schwab, Richard Wennberg, Karl Grenier, Carmela Tartaglia, Charles Tator, Lili-Naz Hazrati
Summary: In this cohort of 35 former collision sports athletes, no significant associations were found between career duration, position played, and role played, and the presence of CTE at autopsy. While limited by the small and nonrepresentative sample studied, these findings suggest that nonsport factors may play a role in determining differing susceptibilities among athletes to CTE.
Article
Neurosciences
Nicole Schwab, YoungJun Ju, Lili-Naz Hazrati
Summary: Repeated mild traumatic brain injury can cause DNA damage-induced cellular senescence, leading to cognitive impairment and potentially promoting the development of neurodegenerative diseases.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
Priti Gros, Xuesong Wang, Jun Guan, Anthony E. Lang, Peter C. Austin, Blayne Welk, Naomi P. Visanji, Connie Marras
Summary: This study compared the association between increased use of phosphoglycerate kinase 1 activators and tamsulosin with Parkinson's disease incidence, finding that both were associated with slight reductions in Parkinson's disease incidence.
MOVEMENT DISORDERS
(2021)
Letter
Clinical Neurology
Richard Wennberg, Nicole Schwab, Lili-Naz Hazrati
Letter
Clinical Neurology
Richard Wennberg, Nicole Schwab, Lili-Naz Hazrati
Review
Clinical Neurology
Naomi P. Visanji, Gabor G. Kovacs, Anthony E. Lang
MOVEMENT DISORDERS CLINICAL PRACTICE
(2021)
Letter
Clinical Neurology
Ivan Martinez-Valbuena, Naomi P. Visanji, Diana A. Olszewska, Mario Sousa, Puja Bhakta, Anna Vasilevskaya, Chloe Anastassiadis, Maria Carmela Tartaglia, Gabor G. Kovacs, Anthony E. Lang
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Xuelin Tang, Paulina Gonzalez-Latapi, Connie Marras, Naomi P. Visanji, Wanli Yang, Christine Sato, Anthony E. Lang, Ekaterina Rogaeva, Ming Zhang
Summary: This study demonstrates for the first time that DNAm-age acceleration is associated with the age at onset of Parkinson's disease, and the faster-aging group has a higher risk.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Seojin Lee, Ivan Martinez-Valbuena, Carlos E. de Andrea, Maria Villalba-Esparza, Suganthini Ilaalagan, Blas Couto, Naomi P. Visanji, Anthony E. Lang, Gabor G. Kovacs
Summary: This study provides the first cell type-specific evaluation of iron homeostasis and oxygen homeostasis in relation to tau pathology in patients with progressive supranuclear palsy (PSP). Astrocytes were identified as the major cell type accumulating iron in the early affected regions of PSP, highly associated with tau pathology. Dysregulated expression of iron and oxygen homeostasis genes associated with brain aging was also found, as well as dysregulated expression of rare neurodegeneration with brain iron accumulation (NBIA) genes associated with tau pathology, distinguishing PSP from the healthy aging brain.
ANNALS OF NEUROLOGY
(2023)
Review
Geriatrics & Gerontology
Mitchell Ng, Lili-Naz Hazrati
Summary: Biological sex plays an important role in many diseases, with distinct differences between men and women in disease development. Cellular senescence may underlie these sex differences and could be a driver of sex-specific disease outcomes. Further research is needed to investigate sex differences in cellular senescence and validate findings from animal studies in human contexts.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Syeda Hania Qamar, Naomi P. P. Visanji
MOVEMENT DISORDERS
(2023)