Article
Biochemistry & Molecular Biology
Yulia S. Spivak, Anna A. Karan, Yulia Dobryakova, Tatiana M. Medvedeva, Vladimir A. Markevich, Alexey P. Bolshakov
Summary: In this study, the effects of stimulation of the medial septal area on gene expression in the dorsal and ventral hippocampus were investigated. The results showed that stimulation of the medial septal nucleus led to a significant increase in the expression of immediate early genes, neurotrophins, and inflammatory cytokines in the ipsilateral dorsal hippocampus. Furthermore, the stimulation of the medial septal nucleus further increased the expression of certain genes in the ipsilateral ventral hippocampus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Hiromi Sano, Atsushi Nambu
Summary: ZNS is an anticonvulsant drug that has beneficial effects on Parkinson's disease and its side effect, L-DOPA-induced dyskinesia, but can also have adverse effects.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Neurosciences
Zhihua Liu, Aijuan Yan, Jiahao Zhao, Shuyuan Yang, Lu Song, Zhenguo Liu
Summary: The study revealed the important role of p75NTR in patients with Parkinson's disease and suggested it as a new target for managing L-dopa-induced dyskinesia.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yulia V. Dobryakova, Konstantin Gerasimov, Yulia S. Spivak, Tinna Korotkova, Alena Koryagina, Angelina Deryabina, Vladimir A. Markevich, Alexey P. Bolshakov
Summary: We investigated the effects of stimulating the dorsal medial septal area (dMSA) on early gene expression in hippocampal cells, leading to long-term potentiation. Rats were implanted with stimulating electrodes in the ventral hippocampal commissure and dMSA, and a recording electrode in the CA1 area. High-frequency stimulation (HFS) of the dMSA induced long-term potentiation in the ventral hippocampal commissure synapses on hippocampal CA1 neurons. Gene expression analysis revealed an increase in bdnf and cyr61 expression in the ipsilateral hippocampus, and egr1 expression in the contralateral ventral hippocampus. Thus, dMSA HFS enhances the expression of specific early genes in the hippocampus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Chemical
Khian Giap Lim, Arunachalam Muthuraman
Summary: This study evaluated the ameliorative effect of beta-carotene in a rat model of diabetic vascular dementia. The results showed that beta-carotene improved cognitive function and normalized neurotransmitter changes, suggesting its potential as a therapeutic agent for the management of vascular dementia.
Article
Biochemistry & Molecular Biology
Tung-Tai Kuo, Yuan-Hao Chen, Vicki Wang, Eagle Yi-Kung Huang, Kuo-Hsing Ma, Nigel H. H. Greig, Jin Jung, Ho- Choi, Lars Olson, Barry J. J. Hoffer, Kuan-Yin Tseng
Summary: This study evaluated the efficacy of PT320 on L-DOPA-induced dyskinetic behaviors and neurochemistry in a progressive Parkinson's disease MitoPark mouse model. The results showed that early administration of PT320 significantly reduced the severity of L-DOPA-induced abnormal involuntary movements, particularly in excessive standing and abnormal paw movements. However, late administration of PT320 did not improve any L-DOPA-induced dyskinesia measurements. Furthermore, early treatment with PT320 increased both tonic and phasic release of dopamine in striatal slices, indicating its potential role in alleviating L-DOPA-induced dyskinesia in Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Kathryn Lanza, Christopher Bishop
Summary: Parkinson's Disease (PD) and long-term L-DOPA treatment induce plasticity that contributes to L-DOPA-induced dyskinesia (LID), with the dopamine D3 receptor (D3R) emerging as a promising target in LID management due to its upregulation in LID. D3R undergoes dynamic changes in both PD and LID, and recent genetic and pharmacologic tools have helped clarify its role in LID.
Article
Cell & Tissue Engineering
Yuka Kasahara, Daiki Masukawa, Kenta Kobayashi, Miwako Yamasaki, Masahiko Watanabe, Yoshio Goshima
Summary: Neurogenesis in the hippocampus is regulated by L-DOPA and its receptor GPR143 independently of dopamine. Low concentrations of L-DOPA promote neurogenesis, and its effect is abolished in GPR143 gene-deficient mice. Decreased neurogenesis and exacerbated depression-like behavior are observed in adult GPR143 gene-deficient mice, but can be attenuated by replenishment of GPR143 in the hippocampus.
Article
Biochemistry & Molecular Biology
Shuming An, Haiyan Sun, Miao Wu, Danfeng Xie, Su-Wan Hu, Hai-Lei Ding, Jun-Li Cao
Summary: The medial septum glutamatergic neurons exhibit higher activities during wakefulness and mainly promote wakefulness through the transition from NREM sleep to wakefulness. Activation of these neurons enhances wakefulness, while inactivation reduces wakefulness. Moreover, these neurons innervate the lateral hypothalamus glutamatergic neurons, which also promote wakefulness.
Article
Neurosciences
Edgar Pena, Tareq M. Mohammad, Fedaa Almohammed, Tahani AlOtaibi, Shahpar Nahrir, Sheraz Khan, Vahe Poghosyan, Matthew D. Johnson, Jawad A. Bajwa
Summary: Clinical responses to dopamine replacement therapy for individuals with Parkinson's disease (PD) are unpredictable, but changes in MDS-UPDRS motor factor scores and motor cortical magnetoencephalography (MEG) may provide clues for predicting clinical differences. Subject-specific machine learning approaches based on neuroimaging data offer tools to improve prediction of therapeutic outcomes for PD.
FRONTIERS IN HUMAN NEUROSCIENCE
(2021)
Article
Oncology
Dongqin Wu, Di Gao, Haitao Yu, Guilin Pi, Rui Xiong, Huiyang Lei, Xin Wang, Enjie Liu, Jinwang Ye, Huilin Yu, Yang Gao, Ting He, Tao Jiang, Fei Sun, Jingfen Su, Guoda Song, Wenju Peng, Ying Yang, Jian-Zhi Wang
Summary: The study found a causal relationship between tau accumulation and cholinergic neuron impairment in Alzheimer's disease. Overexpression of hTau protein in the medial septum of mice resulted in spatial memory impairment and reduction of cholinergic neurons over time. Treatment with donepezil showed improvement in spatial memory deficits induced by hTau accumulation, potentially suggesting a new disease-modifying effect.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Clinical Neurology
Jose A. Pineda-Pardo, Alvaro Sanchez-Ferro, Mariana H. G. Monje, Nicola Pavese, Jose A. Obeso
Summary: The striatal dopaminergic deficit in Parkinson's disease follows a somatotopically related pattern, with an upper-limb onset and progression to other regions of the striatum. The denervation of the putamen was confirmed in both hemispheres and corresponding hemibodies. The findings suggest a precise somatotopic onset of nigrostriatal denervation in Parkinson's disease.
Article
Neurosciences
Monika Jampolska, Kryspin Andrzejewski, Pawel M. Boguszewski, Katarzyna Kaczynska
Summary: Parkinson's disease affects movement control and can also impair respiration, leading to chronic hypoxia and hypercapnia. In this study, we investigated the respiratory response in a PD model and found that baseline ventilation was reduced, but restored with L-DOPA supplementation. This highlights the potential of dopamine supplementation in improving respiratory function in PD.
Article
Neurosciences
Waijiao Cai, Kazumasa Wakamatsu, Fabio A. Zucca, Qing Wang, Kai Yang, Niyaz Mohamadzadehonarvar, Pranay Srivastava, Hitomi Tanaka, Gabriel Holly, Luigi Casella, Shosuke Ito, Luigi Zecca, Xiqun Chen
Summary: By studying samples of substantia nigra from patients with Parkinson's disease, we found increased ratios of pheomelanin to dopamine in the melanin content, as well as reduced levels of eumelanins derived from both DOPA and dopamine. Additionally, an increase in pheomelanin relative to dopamine pheomelanin was observed in Parkinson's disease. These findings provide insights into the roles of pheomelanin and eumelanin in the pathophysiology of Parkinson's disease.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Geriatrics & Gerontology
Shuyuan Yang, Ying Wan, Na Wu, Lu Song, Zhihua Liu, Jiahao Zhao, Ying Liu, Zhenguo Liu, Jing Gan
Summary: The study shows that L-dopa can restore circadian rhythm disturbances in PD rats by regulating the D1R-ERK1/2-mTOR pathway, improving irregular fluctuations in blood pressure and temperature.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Neurosciences
Eva M. Szego, Chris van den Haute, Lennart Hofs, Veerle Baekelandt, Anke van der Perren, Bjorn H. Falkenburger
Summary: This study found that stimulating the autolysosomal degradation through the Rab7 pathway can reduce cellular impairments induced by alpha Syn and prevent neurodegeneration in PD.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Ana Chegao, Mariana Guarda, Bruno M. Alexandre, Liana Shvachiy, Mariana Temido-Ferreira, Ines Marques-Morgado, Barbara Fernandes Gomes, Rune Matthiesen, Luisa V. Lopes, Pedro R. Florindo, Ricardo A. Gomes, Patricia Gomes-Alves, Joana E. Coelho, Tiago Fleming Outeiro, Hugo Vicente Miranda
Summary: This study found that MGO-induced glycation accelerates PD-like sensorimotor and cognitive alterations and increases the accumulation of α-synuclein in the brain. In addition, the study also found that MGO mainly affects glutamatergic signaling in the midbrain, which may be associated with PD and dopaminergic pathways.
NPJ PARKINSONS DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Kate L. Jordan, David J. Koss, Tiago F. Outeiro, Flaviano Giorgini
Summary: This review highlights the important roles of Rab GTPases in vesicle transport and membrane trafficking, and their implications in the pathogenesis of various diseases. It also provides an overview of the current state of pharmacological targeting of Rabs and discusses the challenges of therapeutically targeting these small proteins in humans, particularly in the context of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Rayne S. S. Magalhaes, Fernanda C. Boechat, Aline A. Brasil, Jose R. M. Neto, Gabriela D. Ribeiro, Luan H. Paranhos, Natalia Neves de Souza, Tuane Vieira, Tiago F. Outeiro, Bianca C. Neves, Elis C. A. Eleutherio
Summary: The research suggests that T6P may offer a new paradigm for cancer treatment based on specific inhibition of HK2, playing a crucial role in the survival and proliferation of cancer cells.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Fiamma A. Buratti, Nicola Boeffinger, Hugo A. Garro, Jesica S. Flores, Francisco J. Hita, Phelippe do Carmo Goncalves, Federico dos Reis Copello, Leonardo Lizarraga, Giulia Rossetti, Paolo Carloni, Markus Zweckstetter, Tiago F. Outeiro, Stefan Eimer, Christian Griesinger, Claudio O. Fernandez
Summary: In this study, we investigated the structural details of alpha S and its role in amyloid fibril assembly and lipid-binding. Our findings demonstrate that the aromaticity at position 39 of alpha S strongly influences its aggregation properties and membrane-bound conformations. This research provides new insights into the physiological and pathological events related to alpha S.
Article
Biology
Eva M. Szego, Laura Malz, Nadine Bernhardt, Angela Roesen-Wolff, Bjoern H. Falkenburger, Hella Luksch
Summary: This study demonstrates that chronic activation of the STING pathway is sufficient to cause degeneration of dopaminergic neurons, which could be significant in Parkinson's disease and other neurodegenerative diseases.
Article
Cell Biology
Kambiz Hassanzadeh, Castrese Morrone, Keivan Akhtari, Ellen Gerhardt, Ludovica Zaccagnini, Tiago Fleming Outeiro, Marco Feligioni
Summary: This study aims to investigate the SUMOylation of alpha-Syn isoforms and its impact on cell death and alpha-Syn aggregation. The results suggest that boosting SUMOylation can prevent alpha-Syn aggregation and promote autophagy, and that alpha-Syn 140 and alpha-Syn 126 undergo SUMOylation while alpha-Syn 112 and 98 do not. Overexpression of the non-SUMOylated isoforms leads to increased toxicity and alpha-Syn aggregation. These findings highlight the importance of SUMOylation in modulating alpha-Syn aggregation and the behavior of alpha-Syn isoforms.
MECHANISMS OF AGEING AND DEVELOPMENT
(2023)
Review
Clinical Neurology
Patrick W. Cullinane, Eduardo de Pablo Fernandez, Annekatrin Konig, Tiago Fleming Outeiro, Zane Jaunmuktane, Thomas T. Warner
Summary: Highly reproducible epidemiological evidence suggests that type 2 diabetes (T2D) increases the risk and progression of Parkinson's disease (PD) and repurposing certain antidiabetic medications for PD treatment shows promise. The high prevalence of T2D highlights the need for personalized antidiabetic treatment in PD patients. However, understanding the mechanistic relation and molecular pathways affected by T2D in the brain is essential. The review focuses on the evidence of T2D-associated dysregulation in peripheral and brain pathways, its impact on neurodegeneration in PD, and the challenges in unraveling the complex relationship between T2D, insulin resistance, and PD.
MOVEMENT DISORDERS
(2023)
Editorial Material
Neurosciences
Tiago Fleming Outeiro, Omar M. El-Agnaf
NEUROBIOLOGY OF DISEASE
(2023)
Article
Oncology
Agathe Quesnel, Nathan Coles, Claudio Angione, Priyanka Dey, Tuomo M. Polvikoski, Tiago F. Outeiro, Meez Islam, Ahmad A. Khundakar, Panagiota S. Filippou
Summary: Raman spectroscopy combined with machine learning can discriminate different grades of gliomas and understand their molecular changes, particularly in glycosylation. This technique holds promise as a tool for assisting glioma diagnosis and evaluation.
Article
Clinical Neurology
Andrea Maier, Lena Schopen, Joana C. Thiel, Katharina Mueller, Bruno Fimm, Joerg B. Schulz
Summary: This study investigated the cognitive function of PoTS patients compared to healthy controls during sitting and active standing, and examined whether leg crossing could improve cognitive function. The results showed that PoTS patients had impaired attention in sitting position and impaired executive function in standing position, and leg crossing did not improve executive function.
CLINICAL AUTONOMIC RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Luca Marsili, Jennifer Sharma, Tiago Fleming Outeiro, Carlo Colosimo
Summary: Stem cell-based therapies (SCT) have potential in treating neurodegenerative disorders, but clinical trials are just starting and results may take several years. SCTs can provide both symptomatic and disease-modifying effects, and may complement molecular therapies in precision medicine.
Article
Biochemistry & Molecular Biology
Jingbo Wang, Sabitha Joseph, Siv Vingill, Ekrem Dere, Lars Tatenhorst, Anja Ronnenberg, Paul Lingor, Christian Preisinger, Hannelore Ehrenreich, Joerg B. Schulz, Judith Stegmueller
Summary: Mutations in the PARK15 gene, which encodes the F-box protein FBXO7, have been linked to Parkinsonian Pyramidal syndrome. This study focused on the effects of FBXO7 deficiency in mice and found that it plays a crucial role in corticostriatal projections and synaptic integrity in the striatum. The study also revealed alterations in various pathways and an increase in striatal dopamine concentrations.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Manuela Cassotta, Hugo Geerts, Lise Harbom, Tiago F. Outeiro, Iosif Pediaditakis, Orly Reiner, Stefan Schildknecht, Jens C. Schwamborn, Jarrod Bailey, Kathrin Herrmann, Helena T. Hogberg
Summary: Parkinson's disease (PD) is a complex neurodegenerative condition with a lack of preventive or curative therapies. New approach methodologies (NAMs) hold potential to advance PD research and reduce the reliance on animal-based studies. Key recommendations to advance PD research include integrating NAMs, learning from other neurodegenerative diseases, increasing data sharing, promoting innovative pilot studies, and accessing philanthropic funding.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Liana Shvachiy, Angela Amaro-Leal, Tiago Outeiro, Vera Geraldes
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)