Article
Biochemistry & Molecular Biology
Anna Stankiewicz, Katarzyna Kaczorowska, Ryszard Bugno, Aneta Koziol, Maria H. Paluchowska, Grzegorz Burnat, Barbara Chruscicka, Paulina Chorobik, Piotr Branski, Joanna M. Wieronska, Beata Duszynska, Andrzej Pilc, Andrzej J. Bojarski
Summary: This study developed a group of 1,2,4-oxadiazole derivatives that exhibited positive allosteric modulatory activity on mGlu(4) receptors. These derivatives were selectively active on mGlu(7) and mGlu(8) receptors and showed anxiolytic- and antipsychotic-like properties.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
William Tanguay, Charles Ducrot, Nicolas Giguere, Marie-Josee Bourque, Louis-Eric Trudeau
Summary: In Parkinson's disease, dopamine neurons in the substantia nigra pars compacta show unique vulnerability due to their large axonal arbors. By inducing partial SNc lesions in neonatal mice, researchers found that adult mice exhibited compensatory axonal sprouting in SNc DA neurons after neuronal loss.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Ella A. Kasanga, Yoonhee Han, Walter Navarrete, Robert McManus, Marla K. Shifflet, Caleb Parry, Arturo Barahona, Fredric P. Manfredsson, Vicki A. Nejtek, Jason R. Richardson, Michael F. Salvatore
Summary: Although GDNF has shown efficacy in alleviating parkinsonian signs in PD patients in preclinical and early clinical studies, later trials did not meet primary endpoints, indicating a need for further investigation. The expression of GFR-alpha 1 and RET, two cognate receptors for GDNF, differed between the striatum and substantia nigra, and their differential expression in nigrostriatal neurons correlated with TH cell loss, suggesting that targeting loss of GDNF receptors may enhance therapeutic efficacy against nigrostriatal neuron loss in PD.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Chemistry, Medicinal
Caitlin N. Kent, Mark G. Fulton, Kaylee J. Stillwell, Jonathan W. Dickerson, Matthew T. Loch, Alice L. Rodriguez, Anna L. Blobaum, Olivier Boutaud, Jerri L. Rook, Colleen M. Niswender, P. Jeffrey Conn, Craig W. Lindsley
Summary: A high throughput screen identified a novel, but weak mGlu(4) PAM compound, which was later optimized to deliver a potent compound with good CNS penetration and enantiopreference. The optimized compound displayed robust efficacy in reversing a rodent preclinical Parkinson's disease model.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Clinical Neurology
Koji Furukawa, Atsushi Shima, Daisuke Kambe, Akira Nishida, Ikko Wada, Haruhi Sakamaki, Kenji Yoshimura, Yuta Terada, Yusuke Sakato, Masahiro Mitsuhashi, Masanori Sawamura, Etsuro Nakanishi, Yosuke Taruno, Hodaka Yamakado, Yasutaka Fushimi, Tomohisa Okada, Yuji Nakamoto, Ryosuke Takahashi, Nobukatsu Sawamoto
Summary: This study investigates the correlation between motor impairments and striatal dopaminergic terminal degeneration and nigral neuromelanin-laden dopamine neuron loss in different stages of Parkinson's disease. The findings suggest that striatal dopaminergic terminal loss is a biomarker for early stage motor impairments, while nigral dopamine neuron loss is a biomarker for advanced stage motor impairments.
ANNALS OF NEUROLOGY
(2022)
Article
Clinical Neurology
Alessandro Tozzi, Miriam Sciaccaluga, Vittorio Loffredo, Alfredo Megaro, Ada Ledonne, Antonella Cardinale, Mauro Federici, Laura Bellingacci, Silvia Paciotti, Elena Ferrari, Antonino La Rocca, Alessandro Martini, Nicola B. Mercuri, Fabrizio Gardoni, Barbara Picconi, Veronica Ghiglieri, Elvira De Leonibus, Paolo Calabresi
Summary: The study identified that alpha-synuclein disrupts dopamine system and striatal synaptic plasticity in early stages of Parkinson's disease. Subchronic treatment with L-DOPA was able to rescue alpha-synuclein-induced alterations, showing the critical role of dysfunctional dopamine system in disease progression.
Article
Chemistry, Multidisciplinary
Jiang-Peng Fan, Hui-Zhen Geng, Ya-Wei Ji, Tao Jia, Jennifer B. Treweek, An-An Li, Chun-Yi Zhou, Viviana Gradinaru, Cheng Xiao
Summary: Key components in the nigrostriatal DA system exhibit distinct aging patterns and may contribute to age-related alterations in locomotion and coordination.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Lisa Klotz, Ralf Enz
Summary: The study analyzed the expression and localization of mGluR7a and mGluR7b in mouse cochlear wholemounts, finding a presynaptic localization of mGluR7a at inner hair cells (IHCs) and co-localization of mGluR7b with mGluR7a at IHC ribbon synapses. The numbers of mGluR7a and mGluR7b puncta were reduced at higher frequencies and in older animals, indicating potential age and frequency-related changes in the cochlea.
Article
Biochemistry & Molecular Biology
Melina Decourt, Eric Balado, Haritz Jimenez-Urbieta, Maureen Francheteau, Pierre-Olivier Fernagut, Marianne Benoit-Marand
Summary: Treatment with dopamine agonists in Parkinson's disease is associated with impulsive and compulsive behaviors. This vulnerability is influenced by individual traits, medication types, and neurodegenerative processes. This study investigates the effect of the dopamine D3/D2 agonist pramipexole and selective nigrostriatal degeneration on repetitive and compulsive-like behaviors in rats.
Article
Neurosciences
Zhuo Wang, Yanjun Huang, Zhihua Zhou, Jian Huang, Yitong He, Pingming Qiu
Summary: This study finds that iron deficiency in the substantia nigra directly contributes to hyperlocomotion and sleep disturbances. By injecting the iron chelator deferiprone into the substantia nigra, researchers successfully reduced the iron content and observed behavioral changes. This study offers a promising direction for research and treatment of iron-related neuropsychiatric diseases.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Clinical Neurology
Alexander Rau, Jonas A. Hosp, Michel Rijntjes, Cornelius Weiller, Elias Kellner, Emir Berberovic, Panteleimon Oikonomou, Wolfgang H. Jost, Marco Reisert, Horst Urbach, Nils Schroeter
Summary: This study aimed to explore the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in different subtypes of MSA. The results showed that cerebellar dysfunction contributes to impaired dexterity in both MSA-C and MSA-P, and may serve as a promising biomarker for disease staging. In contrast, no significant association was found with nigrostriatal dysfunction.
MOVEMENT DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Nick G. Hollon, Elora W. Williams, Christopher D. Howard, Hao Li, Tavish Traut, Xin Jin
Summary: Dopamine encodes cue-reward prediction errors during Pavlovian conditioning, but its role in controlling sequential behavior remains largely unknown. Previous studies primarily use discrete reward-predictive stimuli, and it is still unclear whether dopamine represents action-outcome prediction errors.
Article
Radiology, Nuclear Medicine & Medical Imaging
Hiroto Takahashi, Nobuo Kashiwagi, Atsuko Arisawa, Chisato Matsuo, Hiroki Kato, Hiroyoshi Adachi, Yuta Kajiyama, Hideki Mochizuki, Noriyuki Tomiyama
Summary: The study indicates that MRI and DAT imaging are useful for assessing nigrostriatal changes during the preclinical phase of Parkinson's disease. They can distinguish between RBD and PD, providing insight into the progression of the disease.
BRITISH JOURNAL OF RADIOLOGY
(2022)
Article
Immunology
Martina Mazzocchi, Susan R. Goulding, Noelia Morales-Prieto, Tara Foley, Louise M. Collins, Aideen M. Sullivan, Gerard W. O'Keeffe
Summary: The peripheral administration of Class IIa-specific HDIs may have neuroprotective effects in Parkinson's disease.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Kaczorowska, Anna Stankiewicz, Ryszard Bugno, Maria H. H. Paluchowska, Grzegorz Burnat, Piotr Branski, Paulina Cieslik, Joanna M. Wieronska, Mariusz Milik, Mateusz Nowak, Agnieszka Przybylowicz, Aneta Koziol, Agata Hogendorf, Adam S. S. Hogendorf, Justyna Kalinowska-Tluscik, Beata Duszynska, Andrzej Pilc, Andrzej J. J. Bojarski
Summary: Based on the glutamatergic theory of schizophrenia, a new compound library containing 103 members was synthesized and examined for NAM mGlu(7) activity. Active compounds were found only within the quinazolinone chemotype. The compound 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171) exhibited selective activity against other group III mGlu receptors, satisfactory drug-like properties, and showed antipsychotic-like activity in animal models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Valentina Perosa, Lieke de Boer, Gabriel Ziegler, Ivayla Apostolova, Ralph Buchert, Coraline Metzger, Holger Amthauer, Marc Guitart-Masip, Emrah Duezel, Matthew J. Betts
Review
Clinical Neurology
Peter N. E. Young, Mar Estarellas, Emma Coomans, Meera Srikrishna, Helen Beaumont, Anne Maass, Ashwin V. Venkataraman, Rikki Lissaman, Daniel Jimenez, Matthew J. Betts, Eimear McGlinchey, David Berron, Antoinette O'Connor, Nick C. Fox, Joana B. Pereira, William Jagust, Stephen F. Carter, Ross W. Paterson, Michael Scholl
ALZHEIMERS RESEARCH & THERAPY
(2020)
Review
Clinical Neurology
Alexander J. Ehrenberg, Ayesha Khatun, Emma Coomans, Matthew J. Betts, Federica Capraro, Elisabeth H. Thijssen, Konstantin Senkevich, Tehmina Bharucha, Mehrsa Jafarpour, Peter N. E. Young, William Jagust, Stephen F. Carter, Tammaryn Lashley, Lea T. Grinberg, Joana B. Pereira, Niklas Mattsson-Carlgren, Nicholas J. Ashton, Jorg Hanrieder, Henrik Zetterberg, Michael Scholl, Ross W. Paterson
ALZHEIMERS RESEARCH & THERAPY
(2020)
Article
Geriatrics & Gerontology
Matthew J. Betts, Anni Richter, Lieke de Boer, Jana Tegelbeckers, Valentina Perosa, Valentin Baumann, Rumana Chowdhury, Ray J. Dolan, Constanze Seidenbecher, Bjoern H. Schott, Emrah Duezel, Marc Guitart-Masip, Kerstin Krauel
NEUROBIOLOGY OF AGING
(2020)
Review
Neurosciences
Adam D. Farmer, Adam Strzelczyk, Alessandra Finisguerra, Alexander Gourine, Alireza Gharabaghi, Alkomiet Hasan, Andreas M. Burger, Andres M. Jaramillo, Ann Mertens, Arshad Majid, Bart Verkuil, Bashar W. Badran, Carlos Ventura-Bort, Charly Gaul, Christian Beste, Christopher M. Warren, Daniel S. Quintana, Dorothea Hammerer, Elena Freri, Eleni Frangos, Eleonora Tobaldini, Eugenijus Kaniusas, Felix Rosenow, Fioravante Capone, Fivos Panetsos, Gareth L. Ackland, Gaurav Kaithwas, Georgia H. O'Leary, Hannah Genheimer, Heidi I. L. Jacobs, Ilse Van Diest, Jean Schoenen, Jessica Redgrave, Jiliang Fang, Jim Deuchars, Jozsef C. Szeles, Julian F. Thayer, Kaushik More, Kristl Vonck, Laura Steenbergen, Lauro C. Vianna, Lisa M. McTeague, Mareike Ludwig, Maria G. Veldhuizen, Marijke De Couck, Marina Casazza, Marius Keute, Marom Bikson, Marta Andreatta, Martina D'Agostini, Mathias Weymar, Matthew Betts, Matthias Prigge, Michael Kaess, Michael Roden, Michelle Thai, Nathaniel M. Schuster, Nicola Montano, Niels Hansen, Nils B. Kroemer, Peijing Rong, Rico Fischer, Robert H. Howland, Roberta Sclocco, Roberta Sellaro, Ronald G. Garcia, Sebastian Bauer, Sofiya Gancheva, Stavros Stavrakis, Stefan Kampusch, Susan A. Deuchars, Sven Wehner, Sylvain Laborde, Taras Usichenko, Thomas Polak, Tino Zaehle, Uirassu Borges, Vanessa Teckentrup, Vera K. Jandackova, Vitaly Napadow, Julian Koenig
Summary: Transcutaneous vagus nerve stimulation (tVNS) is gaining interest in basic, translational, and clinical research due to its non-invasive nature. Future studies need to focus on reporting practices, stimulation parameters, and participant safety to advance the field. Additionally, advancements in animal research may have implications for the application of tVNS in humans.
FRONTIERS IN HUMAN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Christopher E. J. Doppler, Martin B. Kinnerup, Corinna Brune, Ezequiel Farrher, Matthew Betts, Tatyana D. Fedorova, Jeppe L. Schaldemose, Karoline Knudsen, Rola Ismail, Aline D. Seger, Allan K. Hansen, Kristian Staer, Gereon R. Fink, David J. Brooks, Adjmal Nahimi, Per Borghammer, Michael Sommerauer
Summary: This study investigated neurodegeneration in the locus coeruleus of Parkinson's disease patients, finding reduced MRI contrast and volume in the locus coeruleus, as well as lower noradrenaline transporter density, with a negative correlation between the two. These results suggest distinct patterns of degeneration in different regions of the locus coeruleus in Parkinson's disease.
Review
Pharmacology & Pharmacy
Edward J. R. Fletcher, Thomas Kaminski, Gareth Williams, Susan Duty
Summary: Parkinson's disease is a progressive neurodegenerative disease with no established disease-modifying drugs, leading to a focus on repurposing strategies. These strategies can save time and costs, reduce failure rates, and have shown effectiveness in identifying suitable drugs for clinical trials in Parkinson's disease research.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Review
Neurosciences
Mareike Ludwig, Christian Wienke, Matthew J. Betts, Tino Zaehle, Dorothea Haemmerer
Summary: This review discusses the effects of taVNS on the LC-NE system and the challenges in assessing these effects, emphasizing how translational approaches between animal and human research can aid in understanding the influence of changes in structure and function of the LCNE system across the human lifespan and in disease.
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
(2021)
Article
Neurosciences
Claire J. Ciampa, Jourdan H. Parent, Theresa M. Harrison, Rebekah M. Fain, Matthew J. Betts, Anne Maass, Joseph R. Winer, Suzanne L. Baker, Mustafa Janabi, Daniella J. Furman, Mark D'Esposito, William J. Jagust, Anne S. Berry
Summary: This study examines the relationship between the neurochemical mechanisms of the locus coeruleus (LC) and vulnerability to Alzheimer's disease (AD) as well as cognitive resilience. The findings suggest that higher LC catecholamine synthesis capacity is associated with lower tau pathology and can mitigate tau's negative effect on memory.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Engineering, Biomedical
Max Duennwald, Philipp Ernst, Emrah Duezel, Klaus Toennies, Matthew J. Betts, Steffen Oeltze-Jafra
Summary: The study aimed to develop an automated pipeline for localizing and segmenting the locus coeruleus to derive quantitative biomarkers of neurodegenerative diseases. Results showed promising performance on healthy aging subjects, but further investigation is needed for Parkinson's disease subjects.
INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY
(2021)
Article
Pharmacology & Pharmacy
Emily Clarke, Pawel Stocki, Elizabeth H. Sinclair, Aziz Gauhar, Edward J. R. Fletcher, Alicja Krawczun-Rygmaczewska, Susan Duty, Frank S. Walsh, Patrick Doherty, Julia Lynn Rutkowski
Summary: Single domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells have been used to shuttle antibodies and other cargos across the blood brain barrier (BBB) to the brain. Fusion of the TXB4 brain shuttle with a TrkB neurotrophin receptor agonist antibody allows the antibody to reach neuroprotective concentrations in the brain parenchyma following systemic administration, showing potent agonist activity at its cognate receptor and preventing the death of dopaminergic neurons in a mouse model of Parkinson's disease.
Article
Neurosciences
Yazead Buhidma, Carl Hobbs, Marzia Malcangio, Susan Duty
Summary: Pain is a significant non-motor feature of Parkinson's disease (PD) that greatly affects quality of life. The mechanisms behind chronic pain in PD are not well understood, leading to a lack of effective treatments. However, studies using a rat model of PD and human PD tissue samples have identified reductions in dopaminergic neurons in the periaqueductal grey (PAG) and Met-enkephalin levels in the dorsal horn of the spinal cord, as well as alterations in downstream serotonergic activity, which may contribute to the manifestation of pain in PD. These findings suggest potential targets for improved pain relief in PD patients.
NPJ PARKINSONS DISEASE
(2023)
Review
Clinical Neurology
Robin Borchert, Tiago Azevedo, AmanPreet Badhwar, Jose Bernal, Matthew Betts, Rose C. Bruffaerts, Michael Burkhart, Ilse M. Dewachter, Helena Gellersen, Audrey Low, Ilianna Lourida, Luiza R. Machado, Christopher Madan, Maura Malpetti, Jhony Mejia, Sofia Michopoulou, Carlos Munoz-Neira, Jack Pepys, Marion Peres, Veronica Phillips, Siddharth Ramanan, Stefano M. Tamburin, Hanz Tantiangco, Lokendra Thakur, Alessandro Tomassini, Ashwati Vipin, Eugene Tang, Danielle Newby, Janice M. Ranson, David J. Llewellyn, Michele Veldsman, Timothy Rittman
Summary: Artificial intelligence (AI) and neuroimaging provide new opportunities for the diagnosis and prognosis of dementia. However, there are methodological limitations in current studies, and there is a need for better model validation and improved descriptions of algorithm development.
ALZHEIMERS & DEMENTIA
(2023)
Meeting Abstract
Clinical Neurology
J. Pape, I. Galazky, E. Duezel, M. J. Betts
PARKINSONISM & RELATED DISORDERS
(2020)
Correction
Geriatrics & Gerontology
Kathy Y. Liu, Julio Acosta-Cabronero, Arturo Cardenas-Blanco, Clare Loane, Alex J. Berry, Matthew J. Betts, Rogier A. Kievit, Richard N. Henson, Emrah Duezel, Robert Howard, Dorothea Hammerer
NEUROBIOLOGY OF AGING
(2020)