Article
Clinical Neurology
Marta Gonzalez-Sepulveda, Joan Compte, Thais Cuadros, Alba Nicolau, Camille Guillard-Sirieix, Nuria Penuelas, Marina Lorente-Picon, Annabelle Parent, Jordi Romero-Gimenez, Joana M. Cladera-Sastre, Ariadna Laguna, Miquel Vila
Summary: Neurons that accumulate the highest levels of neuromelanin with age are also the most susceptible to degeneration in Parkinson's disease. Using a neuromelanin-producing rat model, Gonzalez-Sepulveda, Compte et al. show that slowing down age-dependent neuromelanin production can help prevent Parkinson's disease-like features.
Article
Neurosciences
Rosaria Formisano, Katarzyna D. Rosikon, Abhyudai Singh, Harbinder S. Dhillon
Summary: The study examined the mechanisms of dopamine release and clearance, finding that DAT-1 acts as a negative feedback modulator in regulating neurotransmitter vesicle fusion. Through experimental results and a mechanistic model, the dynamics of synaptic vesicle fusion were dissected, and the feedback effects of DAT-1 were compared with dopamine auto-receptors. The findings have broader significance as similar dynamics may be utilized by other synaptic modulators across species.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Joseph Wayne M. Fowler, Nabil E. Boutagy, Rong Zhang, Daiki Horikami, Michael B. Whalen, Casey E. Romanoski, William C. Sessa
Summary: The transcription factor SREBP2 is the main regulator of cholesterol homeostasis and has been implicated in leukocyte immune responses. In this study, the role of SREBP2 in endothelial cells was investigated, revealing its impact on inflammatory chemokine production and interferon response genes.
JOURNAL OF LIPID RESEARCH
(2023)
Review
Cell Biology
Joanne Ng, Serena Barral, Simon N. Waddington, Manju A. Kurian
Summary: Infantile parkinsonism-dystonia due to dopamine transporter deficiency syndrome (DTDS) is an ultrarare childhood movement disorder caused by biallelic loss-of-function mutations in the SLC6A3 gene. Advances in genomic analysis have revealed an evolving spectrum of SLC6A3-related neurological and neuropsychiatric disorders. In this review, we provide an overview of the expanding clinical phenotype of DTDS and the precision therapies in development, including pharmacochaperones and gene therapy.
Article
Biochemistry & Molecular Biology
Jessica IChi Lai, Alessandra Porcu, Benedetto Romoli, Maria Keisler, Fredric P. P. Manfredsson, Susan B. B. Powell, Davide Dulcis
Summary: This study investigated the mechanism of how nicotine-induced dopamine (DA) plasticity protects substantia nigra (SN) neurons against nigrostriatal damage in Parkinson's disease (PD). The results showed that chronic nicotine treatment led to upregulation of transcription factor Nurr1 and DA-synthesizing enzyme tyrosine hydroxylase (TH) in GABAergic neurons in the SN. Nicotine also reduced the number of alpha-synuclein-expressing neurons and rescued motor deficits in PD mice. Importantly, the activation of GABA neurons and Nurr1 overexpression were sufficient to mimic nicotine-mediated dopamine plasticity. This study provides insights into developing new strategies for neurotransmitter replacement in PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Seong Ho Jeong, Namki Hong, Hye Sun Lee, Sookyeong Han, Young-gun Lee, Yoonju Lee, Yumie Rhee, Young H. Sohn, Phil Hyu Lee
Summary: This study found that skull bone density in female PD patients is associated with disease progression and motor impairments, especially in younger patients.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Isabelle M. Capell-Hattam, Nicole M. Fenton, Hudson W. Coates, Laura J. Sharpe, Andrew J. Brown
Summary: In this study, researchers identified the noncatalytic protein ERG28 as a player in mammalian cholesterol synthesis. They found that ERG28 is transcriptionally regulated by the transcription factor SREBP-2 and interacts with enzymes involved in cholesterol synthesis. Knockout of ERG28 resulted in reduced cholesterol levels and impaired cholesterol synthesis. Additionally, ERG28 knockout also affected the activation of SREBP-2 under sterol-replete conditions. These findings highlight the importance of ERG28 in cholesterol synthesis and suggest that further understanding of this protein could contribute to therapeutic strategies for diseases associated with aberrant cholesterol metabolism.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biology
Dino Luethi, Julian Maier, Deborah Rudin, Daniel Szollosi, Thomas J. F. Angenoorth, Stevan Stankovic, Matthias Schittmayer, Isabella Burger, Jae-Won Yang, Kathrin Jaentsch, Marion Holy, Anand Kant Das, Mario Brameshuber, Gisela Andrea Camacho-Hernandez, Andrea Casiraghi, Amy Hauck Newman, Oliver Kudlacek, Ruth Birner-Gruenberger, Thomas Stockner, Gerhard J. Schutz, Harald H. Sitte
Summary: This study investigates the subunit stoichiometry and function of the plasmalemmal norepinephrine transporter (NET), showing the direct regulation of NET organization and function by phosphatidylinositol 4,5-bisphosphate (PIP2).
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Raza Abbas Mahdi, Israr Ahmad, Talha Jilani, Jamal Akhtar Ansari, Farzana Mahdi, Abbas Ali Mahdi, Tabrez Jafar
Summary: The study investigated dopamine gene polymorphism, biochemical and oxidative stress parameters in elderly patients with and without depression. Changes in levels of various markers including dopamine, antioxidants and oxidative stress markers were observed in depressed individuals compared to controls, suggesting a possible association between these factors and depression in the aging population.
INDIAN JOURNAL OF CLINICAL BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jen-Zen Chuang, Nan Yang, Nobuyuki Nakajima, Wataru Otsu, Cheng Fu, Howard Hua Yang, Maxwell Ping Lee, Armaan Fazal Akbar, Tudor Constantin Badea, Ziqi Guo, Afnan Nuruzzaman, Kuo-Shun Hsu, Joshua L. Dunaief, Ching-Hwa Sung
Summary: In this study, researchers observed that mice lacking chloride intracellular channel 4 in retinal pigment epithelium exhibited a full spectrum of functional and pathological features of dry AMD, including drusen formation. Multidisciplinary longitudinal studies revealed a mechanistic link between RPE cell-autonomous aberrant lipid metabolism and transport and drusen formation.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Yueyue Liu, Qiaoying Huang, Zijian Wei, Shanshan Ma, James R. Woodgett, Mingtao Li, Junyu Li
Summary: The study demonstrates that in a MPTP-induced mouse model of Parkinson's disease, p62 translocates from the cytoplasm to the nucleus, which is detrimental to nigral dopaminergic neurons. GSK-3 mediates the nuclear translocation of p62 and plays a crucial role in PD neurodegeneration.
NEUROSCIENCE LETTERS
(2021)
Article
Neurosciences
Erika Iori, Marco Mazzoli, Alessandra Ariatti, Tiziana Salviato, Vittorio Rispoli, Franco Valzania, Giuliana Galassi
Summary: This study retrospectively analyzed the cases of 12 patients with both Parkinson's disease (PD) and Myasthenia Gravis (MG). The study found that male gender and multiple comorbidities were more common in patients with MG associated with PD. Most cases showed a benign clinical course, but a few cases experienced worsening. This suggests that MG and PD may evolve independently.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Rohan Gupta, Pravir Kumar
Summary: Integrating omics data to decipher the biological regulatory network can reveal potential mechanisms of complex diseases like Alzheimer's and Parkinson's. The acetylation mechanism and HDAC enzymes play a crucial role in studying the shared phenomenon between AD and PD pathogenesis. The study highlights the importance of proteins, transcription factors, lysine residues, and HDAC enzymes shared between AD and PD, providing valuable insights for molecular studies on the AD-PD crosstalk.
Review
Biochemistry & Molecular Biology
Avner Schlessinger, Nicole Zatorski, Keino Hutchinson, Claire Colas
Summary: Solute carrier (SLC) transporters play a significant role in transporting solutes across biological membranes. Their dysregulation is associated with various diseases, making them important targets for therapeutic intervention. Recent advancements in experimental and computational techniques have greatly contributed to SLC research and drug discovery. This review focuses on emerging topics in therapeutic discovery of SLCs, highlighting state-of-the-art approaches and discussing current challenges in transporter drug discovery.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Geriatrics & Gerontology
Jared T. Hinkle, Kelly A. Mills, Kate Perepezko, Gregory M. Pontone
Summary: The study found that striatal dopamine function is associated with motivational dysregulation in PD patients, with elevated right striatal VMAT2 in the ICD group and reduced in the apathy group. Normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally.
JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY
(2022)
Article
Cell Biology
Marie-Laure Arotcarena, Federico N. Soria, Anthony Cunha, Evelyne Doudnikoff, Geoffrey Prevot, Jonathan Daniel, Mireille Blanchard-Desce, Philippe Barthelemy, Erwan Bezard, Sylvie Crauste-Manciet, Benjamin Dehay
Summary: Researchers have discovered that acidic nanoparticles can improve neurodegeneration and restore lysosomal function in Parkinson's disease, offering a new treatment strategy for this and other age-related proteinopathies.
Article
Clinical Neurology
Margaux Teil, Sandra Dovero, Mathieu Bourdenx, Marie-Laure Arotcarena, Sandrine Camus, Gregory Porras, Marie-Laure Thiolat, Ines Trigo-Damas, Celine Perier, Cristina Estrada, Nuria Garcia-Carrillo, Michele Morari, Wassilios G. Meissner, Maria Trinidad Herrero, Miquel Vila, Jose A. Obeso, Erwan Bezard, Benjamin Dehay
Summary: Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, are characterized by the deposit of alpha-synuclein aggregates in neurons and glial cells. A study found that inoculating brain fractions containing glial cytoplasmic inclusions from multiple system atrophy patients into non-human primates resulted in neurodegeneration, oligodendrocyte loss, demyelination, neuroinflammation and alpha-synuclein pathology. These findings suggest the potential use of this experimental model for multiple system atrophy research and therapy development.
Article
Pharmacology & Pharmacy
Anthony Cunha, Alexandra Gaubert, Julien Verget, Marie-Laure Thiolat, Philippe Barthelemy, Benjamin Dehay
Summary: This study proposes a new pharmaceutical technology that delivers trehalose using nanotechnology to restore autophagy function and treat neurodegenerative diseases.
Article
Neurosciences
Margaux Teil, Evelyne Doudnikoff, Marie-Laure Thiolat, Sylvain Bohic, Erwan Bezard, Benjamin Dehay
Summary: The study investigated the effects of zinc modulation on the progression of Parkinson's disease, and found that pharmacological chelation of zinc can attenuate PD-related pathological changes and dopaminergic neuronal degeneration, suggesting zinc chelation as a potential disease-modifying strategy for treating PD.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Morgane Darricau, Taxiarchis Katsinelos, Flavio Raschella, Tomislav Milekovic, Louis Crochemore, Qin Li, Gregoire Courtine, William A. McEwan, Benjamin Dehay, Erwan Bezard, Vincent Planche
Summary: This study demonstrates that progressive supranuclear palsy (PSP) patient-derived tau aggregates can induce motor and behavioral impairments in non-human primates, showing characteristics of prion-like seeding and spreading of PSP lesions. This pilot study paves the way for using PSP tau-injected macaques as a relevant animal model to accelerate drug development for this rare and fatal neurodegenerative disease.
Review
Neurosciences
Juan Estaun-Panzano, Marie-Laure Arotcarena, Erwan Bezard
Summary: Synucleinopathies are a group of diseases characterized by the misfolding and aggregation of alpha-synuclein, leading to the formation of Lewy bodies. Studying the aggregation of alpha-synuclein is crucial for understanding these diseases, and recent breakthroughs have provided new insights into their mechanisms.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemical Research Methods
Benjamin Dehay, Valerie Desvergnes, Mathias Brouillard, Remi Kinet, Marie Joyeux, Sylvie Crauste-Manciet
Summary: The multimerization of active compounds is a successful strategy for addressing the multivalency of biological targets. Carrying multiple active ingredient units on the same scaffold improves drug delivery and biological activity. In this study, tetrameric nanocarriers were synthesized to release four biocompatible units with better in vivo stability and therapeutic efficiency than monomeric molecules. The results suggest that multimeric compounds have therapeutic opportunities and better tolerance compared to monomers.
BIOCONJUGATE CHEMISTRY
(2023)
Review
Neurosciences
Erwan Bezard, David Gray, Rouba Kozak, Matthew Leoni, Cari Combs, Sridhar Duvvuri
Summary: Currently available therapeutics for PD do not provide sustained and predictable relief from motor symptoms without significant adverse events (AEs). There is a need for a treatment that can effectively relieve motor symptoms with reduced risk of AEs.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Article
Biochemical Research Methods
Ibrahim Kaya, Luke S. Schembri, Anna Nilsson, Reza Shariatgorji, Sooraj Baijnath, Xiaoqun Zhang, Erwan Bezard, Per Svenningsson, Luke R. Odell, Per E. Andren
Summary: This study presents an on-tissue chemical derivatization MALDI mass spectrometry imaging approach for the comprehensive mapping of carboxyls and aldehydes in brain tissue sections. The approach successfully detected and imaged various carboxyl and aldehyde-containing endogenous metabolites simultaneously. The methodology provides a powerful tool for sensitive and simultaneous spatial molecular imaging of numerous aldehydes and carboxylic acids during pathological states in brain tissue.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Clinical Neurology
Miguel Lopez-Cuina, Paul Guerin, Nathalie Dutheil, Christelle Martin, Thierry Leste Lasserre, Pierre-Olivier Fernagut, Wassilios G. Meissner, Erwan Bezard
Summary: This study demonstrates that lowering brain GRK2 levels through delivery of a GRK2-specific miRNA can reverse central nervous system insulin resistance and provide neuroprotection in a mouse model of multiple system atrophy. These findings suggest that GRK2 may be a potential therapeutic target for the treatment of MSA.
MOVEMENT DISORDERS
(2023)
Review
Cell Biology
Remi Kinet, Benjamin Dehay
Summary: The aging population and lack of curative treatment for Parkinson's disease pose essential challenges in the coming years, making research crucial for therapeutic developments. Advances in understanding this neurodegenerative disorder have led to the discovery of new pathogenesis-related genes through genome-wide association analysis. Additionally, recent insights into the connection between Parkinson's disease and disrupted autophagy mechanisms have allowed the development of animal models mimicking autophagic dysregulation, providing opportunities to explore potential therapeutic strategies for restoring autophagy activity.
Article
Neurosciences
Ibrahim Kaya, Anna Nilsson, Dominika Luptakova, Yachao He, Theodosia Vallianatou, Patrik Bjarterot, Per Svenningsson, Erwan Bezard, Per E. Andren
Summary: Metabolism of MPTP leads to the neurotoxin MPP+, which causes Parkinson's disease-like symptoms by destroying dopaminergic neurons in the brain. This study used mass spectrometry imaging to analyze glycerophospholipids and sphingolipids in monkey brains and found dysregulation of sulfatide metabolism in the MPTP-lesioned brain regions. Depletion of long-chain hydroxylated sulfatides suggests oxidative stress and damage to myelin in these regions. These findings contribute to our understanding of the molecular pathology of MPTP-induced parkinsonism and provide a basis for further research on dysregulated sulfatide metabolism in Parkinson's disease.
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
Margaux Teil, Sandra Dovero, Mathieu Bourdenx, Marie-Laure Arotcarena, Morgane Darricau, Gregory Porras, Marie-Laure Thiolat, Ines Trigo-Damas, Celine Perier, Cristina Estrada, Nuria Garcia-Carrillo, Maria Trinidad Herrero, Miquel Vila, Jose A. Obeso, Erwan Bezard, Benjamin Dehay
Summary: This study demonstrates the potential of α-syn pathological propagation and neuronal loss in non-human primates by injecting LB fractions from PD patients into the cortex. This provides novel data and a possible primate model of DLB.
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
E. A. Kelly, T. M. Love, J. L. Fudge
Summary: Dopamine is involved in stress-related illnesses, and corticotropin-releasing factor plays a role in stress responses. This study examined the synaptic terminals between dopamine and non-dopamine cells and found that dopamine regulation may occur indirectly through contacts with non-dopamine neurons.
