Article
Neurosciences
Xuan Wang, Zhenfeng Shu, Quansheng He, Xiaowen Zhang, Luozheng Li, Xiaoxue Zhang, Liang Li, Yujie Xiao, Bo Peng, Feifan Guo, Da-Hui Wang, Yousheng Shu
Summary: This study found that parvalbumin neurons in the striatum have functional autapses, while principal spiny projection neurons do not. The autaptic responses in parvalbumin neurons are mediated by GABA(A) receptors and regulate their spiking activity. These autapses may play important roles in striatal functions.
NEUROSCIENCE BULLETIN
(2023)
Review
Cell Biology
Yinghong Dai, Haonan Wang, Aojie Lian, Jinchen Li, Guihu Zhao, Shenghui Hu, Bin Li
Summary: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG trinucleotide repeat sequence in the HTT gene. It is characterized by involuntary dance-like movements and severe mental disorders. Mitochondrial dysfunction plays an important role in the pathogenesis of HD. This review discusses the role of mitochondrial dysfunction in HD in terms of bioenergetics, abnormal autophagy, and abnormal mitochondrial membranes, providing researchers with a more comprehensive understanding of the relationship between mitochondrial dysregulation and HD.
Review
Biochemistry & Molecular Biology
Annalisa Tassone, Maria Meringolo, Giulia Ponterio, Paola Bonsi, Tommaso Schirinzi, Giuseppina Martella
Summary: Strong evidence suggests that the decline in mitochondrial function is correlated with degenerative diseases. Various types of neurodegenerative diseases, such as Huntington's chorea and Parkinson's disease, share mitochondrial bioenergy dysregulation as a common feature. These diseases have different manifestations and genetic factors, but they both involve neuronal dysfunction and striatal impairment. This review focuses on describing the onset and development of both diseases in relation to mitochondrial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Marion Ciancia, Monika Rataj-Baniowska, Nicolas Zinter, Vito Antonio Baldassarro, Valerie Fraulob, Anne-Laure Charles, Rosana Alvarez, Shin-ichi Muramatsu, Angel R. de Lera, Bernard Geny, Pascal Dolle, Anna Niewiadomska-Cimicka, Wojciech Krezel
Summary: Retinoic acid receptor beta (RAR beta) plays an important role in brain development and neuroprotection of a specific type of neurons called striatopallidal medium spiny neurons (spMSNs). Lack of RAR beta leads to mitochondrial dysfunction and neurodegeneration, making the neurons more vulnerable. In vitro experiments show that an RAR beta agonist can reduce toxicity to striatal neurons, while in vivo experiments show that RAR beta-deficient neurons are more sensitive to a specific mitochondrial toxin. These findings are significant for understanding the role of retinoic acid in brain development and neurodegenerative diseases.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Public, Environmental & Occupational Health
Kathleen Flanagan
Summary: An important insight from Michel Foucault's work is the attention to how medical science shapes subjectivity. This paper uses a Foucauldian analysis to examine the construction of subjectivity in the context of Huntington's disease. The study identifies the key features of the disease, such as its genetic transmission, age of onset, and behavioral symptoms, and explores how medical and psychiatric knowledge has contributed to the stigmatization of affected individuals and their inclusion in eugenicist discourse.
SOCIAL SCIENCE & MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Bindu D. Paul
Summary: Cysteine plays important roles in cellular processes and signaling cascades, and abnormal cysteine and H2S metabolism are associated with Huntington's disease.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Xiaojuan Han, Shengnan Zhao, Hua Song, Tianshu Xu, Qijun Fang, Gang Hu, Linyun Sun
Summary: The study demonstrates that kaempferol prevents dopaminergic neuronal degeneration in Parkinson's disease by inhibiting lipid peroxidation-mediated mitochondrial damage through promoting lipophagy, providing a potential novel therapeutic strategy for Parkinson's disease and related neurodegenerative diseases.
Article
Neurosciences
Ana Fernandez, Carmen Martinez-Ramirez, Ana Gomez, Antonio M. G. de Diego, Luis Gandia, Maria Jose Casarejos, Antonio G. Garcia
Summary: From a pathogenic perspective, Huntington's disease (HD) is considered a synaptopathy with alterations in neurotransmitter release and catecholamine secretion in chromaffin cells (CCs). This study explored the impact of mitochondrial deficits on CCs in a mouse model of HD. The results showed fragmented mitochondria, oxidative stress, decreased respiration and ATP levels, mitochondrial depolarization, and impaired catecholamine release and calcium channel currents. These alterations were observed at an early disease stage, suggesting that mitochondrial dysfunction is a primary event in HD pathogenesis.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Cell Biology
Mathew George, Matthan Tharakan, John Culberson, Arubala P. Reddy, P. Hemachandra Reddy
Summary: Nrf2 is a crucial transcription factor that regulates gene expression in healthy and disease states. It plays a vital role in oxidative stress, mitochondrial function, autophagy, and is closely associated with aging and neurodegenerative diseases.
AGEING RESEARCH REVIEWS
(2022)
Article
Neurosciences
Manli Zhong, Yuhan Wang, Geng Lin, Francesca-Fang Liao, Fu-Ming Zhou
Summary: This study found that in mice, the medium spiny neurons responsible for motor control and cognition in the striatum are not affected by dopamine loss, contrary to previous theories.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Lucas M. Kangussu, Natalia P. Rocha, Priscila A. C. Valadao, Thatiane C. G. Machado, Kivia B. Soares, Julliane V. Joviano-Santos, Leigh B. Latham, Gabriela D. Colpo, Ana Flavia Almeida-Santos, Erin Furr Stimming, Ana Cristina Silva, Antonio L. Teixeira, Aline Silva Miranda, Cristina Guatimosim
Summary: The imbalance of the Renin-Angiotensin System in the central nervous system may play a role in the pathophysiology of Huntington's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Jonathan Gaucher, Guillaume Vial, Emilie Montellier, Maelle Guellerin, Sophie Bouyon, Emeline Lemarie, Veronique Pelloux, Anne Bertrand, Karin Pernet-Gallay, Frederic Lamarche, Anne-Laure Borel, Claire Arnaud, Elise Belaidi, Karine Clement, Diane Godin Ribuot, Judith Aron-Wisnewsky, Jean-Louis Pepin
Summary: Sleep Apnea Syndrome (SAS), a common chronic disease affecting nearly one billion people worldwide, has been found to be an independent risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD) through the occurrence of intermittent hypoxia (IH). This study revealed that IH reprograms gene expression and increases the oxidative capacity of liver mitochondria, leading to an imbalance between oxidative stress and antioxidant defense, which in turn contributes to the development of liver disease. These findings provide insights into the mechanisms underlying NAFLD development during SAS and suggest potential therapeutic targets and biomarkers.
FRONTIERS IN MEDICINE
(2022)
Article
Clinical Neurology
Emily Sun, Matthew Kang, Pierre Wibawa, Vivian Tsoukra, Zhibin Chen, Sarah Farrand, Dhamidhu Eratne, Wendy Kelso, Andrew Evans, Mark Walterfang, Dennis Velakoulis, Samantha M. Loi
Summary: This is the first study to examine risk factors associated with mortality in Huntington's Disease (HD) in an Australian cohort. The median survival in our cohort is consistent with previous studies, and significantly reduced compared to the general Australian population. CAG repeat length is not correlated with mortality, suggesting that non-genetic factors contribute to mortality status.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Carlos Estevez-Fraga, Andre Altmann, Christopher S. Parker, Rachael Scahill, Beatrice Costa, Zhongbo Chen, Claudia Manzoni, Angeliki Zarkali, Alexandra Durr, Raymund A. C. Roos, Bernhard Landwehrmeyer, Blair R. Leavitt, Geraint Rees, Sarah J. Tabrizi, Peter McColgan
Summary: Cortical cell loss in premanifest Huntington's disease is associated with the expression of developmental and neurodegenerative genes, with astrocytes and endothelial cells enriched in the developmental profile and neurons and microglia enriched in the neurodegenerative profile.
Article
Neurosciences
Naemeh Pourshafie, Ester Masati, Amber Lopez, Eric Bunker, Allison Snyder, Nancy A. Edwards, Audrey M. Winkelsas, Kenneth H. Fischbeck, Christopher Grunseich
Summary: This study found that SYNJ2BP is increased in diseased motor neurons and under stress in iPSC-derived motor neurons. Proteomic analysis showed that elevated SYNJ2BP alters the distribution of mitochondria and increases mitochondrial-ER membrane contact sites. Additionally, decreasing SYNJ2BP levels improves mitochondrial oxidative function in diseased motor neurons.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
L. J. McMeekin, A. F. Bartley, A. S. Bohannon, E. W. Adlaf, T. van Groen, S. M. Boas, S. N. Fox, P. J. Detloff, D. K. Crossman, L. S. Overstreet-Wadiche, J. J. Hablitz, L. E. Dobrunz, R. M. Cowell
Article
Chemistry, Medicinal
Bini Mathew, Pedro Ruiz, Shilpa Dutta, Jordan T. Entrekin, Sixue Zhang, Kaval D. Patel, Micah S. Simmons, Corinne E. Augelli-Szafran, Rita M. Cowell, Mark J. Suto
Summary: ALS is a rare neurodegenerative disease with unknown cause, characterized by the gradual degeneration of motor neurons. Mutations in SOD1 and SOD2 genes are associated with ALS. Research has shown that hybrid compounds of SRI-22819 and Ataluren may have improved therapeutic effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Neurosciences
Nolwazi Z. Gcwensa, Dreson L. Russell, Rita M. Cowell, Laura A. Volpicelli-Daley
Summary: Parkinson's disease is a progressive neurodegenerative disease with no treatment to slow its progression. Evidence suggests that synaptic impairments may precede neuronal cell loss, highlighting the need for novel therapeutics targeting the synapse. Genetic studies implicate several genes in synaptic dysfunction in PD, and future studies should explore the roles of implicated genes across multiple neuron types and circuits.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Joshua M. Marcus, Mohammed I. Hossain, Jean-Philippe Gagne, Guy G. Poirier, Lori L. McMahon, Rita M. Cowell, Shaida A. Andrabi
Summary: This study revealed that the cytosolic translocation of TDP-43 in neurodegenerative disease depends on activation of PARP-1, and suggested that PARP inhibitors could have a neuroprotective role in diseases involving TDP-43.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Neurosciences
Connie Mackenzie-Gray Scott, R. Ryley Parrish, Darren Walsh, Claudia Racca, Rita M. Cowell, Andrew J. Trevelyan
Summary: The study demonstrates that knocking down the transcriptional coactivator PGC-1 alpha in PV-expressing cells in the cortical network produces an antiepileptic effect, reducing the activity of epileptic discharges and extending the period before the onset of seizure events.
JOURNAL OF NEUROPHYSIOLOGY
(2022)
Article
Neurosciences
Allison R. Fusilier, Jennifer A. Davis, Jodi R. Paul, Stefani D. Yates, Laura J. McMeekin, Lacy K. Goode, Mugdha Mokashi, Natalie Remiszewski, Thomas van Groen, Rita M. Cowell, Lori L. McMahon, Erik D. Roberson, Karen L. Gamble
Summary: Research has shown disrupted circadian gene regulation, hippocampal physiology, and memory in AD mouse models, providing insights into possible chronotherapeutic strategies to ameliorate Alzheimer's disease symptoms or delay pathological onset.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
L. J. McMeekin, K. L. Joyce, L. M. Jenkins, B. M. Bohannon, K. D. Patel, A. S. Bohannon, A. Patel, S. N. Fox, M. S. Simmons, J. J. Day, A. Kralli, D. K. Crossman, R. M. Cowell
Summary: This study identified ERRa as necessary for normal expression of PGC-1a-dependent genes in neurons, with a strong correlation in expression between ERRa and PGC-1a in the brain. In ERRa null mice, PGC-1a-dependent genes were reduced in multiple brain regions, leading to behavioral abnormalities without severe motor impairments seen in PGC-1a null mice.
Review
Biochemistry & Molecular Biology
Stephanie M. Boas, Kathlene L. Joyce, Rita M. Cowell
Summary: This article reviews the biology of NFE2/NRF transcription factor family in the brain and the cellular localization of NFE2/NRF family members in nervous system cells. It discusses the relationship between these findings and oxidative stress observed in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and presents strategies for activating NFE2/NRF-dependent transcription. Based on the expression of NFE2/NRF family members in specific populations of neurons and glia, the authors propose considering the relative contributions of different cell types to the overall oxidative state when designing neuroprotection strategies.
Correction
Neurosciences
L. J. McMeekin, K. L. Joyce, L. M. Jenkins, B. M. Bohannon, K. D. Patel, A. S. Bohannon, A. Patel, S. N. Fox, M. S. Simmons, J. J. Day, A. Kralli, D. K. Crossman, R. M. Cowell
Article
Biochemistry & Molecular Biology
Gelare Ghajar-Rahimi, Amie M. Traylor, Bini Mathew, James R. Bostwick, N. Miranda Nebane, Anna A. Zmijewska, Stephanie K. Esman, Saakshi Thukral, Ling Zhai, Vijaya Sambandam, Rita M. Cowell, Mark J. Suto, James F. George, Corinne E. Augelli-Szafran, Anupam Agarwal
Summary: Acute kidney injury is a major health concern with no current effective treatments. This study identifies small-molecule inducers of HO-1 as potential therapeutic candidates for AKI.
Article
Neurosciences
S. N. Fox, L. J. McMeekin, C. H. Savage, K. L. Joyce, S. M. Boas, M. S. Simmons, C. B. Farmer, J. Ryan, L. Pereboeva, K. Becker, J. Auwerx, S. Sudarshan, J. Ma, A. Lee, R. C. Roberts, D. K. Crossman, A. Kralli, R. M. Cowell
Summary: ERR γ plays a crucial role in dopaminergic neurons and its deficiency is associated with reductions in mitochondrial function, synaptic genes, and autophagy-related genes, potentially serving as a model for PD.
NPJ PARKINSONS DISEASE
(2022)
Article
Neurosciences
Mahendra Singh, Kiran Sapkota, Kenji Sakimura, Masanobu Kano, Rita M. Cowell, Linda Overstreet-Wadiche, John J. Hablitz, Kazu Nakazawa
Summary: Hypofunction of the NMDAR receptor during brain development may contribute to the onset of schizophrenia in young adults. The cellular targets of NMDAR hypofunction include corticolimbic fast-spiking interneurons. However, the functional alterations in PV-positive FS interneurons following NMDAR hypofunction are not well understood.
Correction
Neurosciences
Mark S. Moehle, Philip J. Webber, Tonia Tse, Nour Sukar, David G. Standaert, Tara M. DeSilva, Rita M. Cowell, Andrew B. West
JOURNAL OF NEUROSCIENCE
(2022)
Article
Clinical Neurology
Dorian Sargent, Lindsey A. Cunningham, Dylan J. Dues, Yue Ma, Jennifer J. Kordich, Gabriela Mercado, Patrik Brundin, Rita M. Cowell, Darren J. Moore
Summary: Neurodegenerative diseases are characterized by the degeneration of neuronal populations in different brain regions and the formation of protein aggregates. VPS35 is implicated in many neurodegenerative diseases and plays a critical role in neuronal viability.
BRAIN COMMUNICATIONS
(2021)