Review
Genetics & Heredity
Xiangzhen Wei, Menghua Cai, Lifang Jin
Summary: Parkinson's disease is a chronic degenerative disease of the central nervous system, mainly affecting the motor system. Studies have shown that Parkinson's disease involves epigenetic mechanisms such as DNA methylation and histone modification. Some metals may induce Parkinson's disease by modulating epigenetic mechanisms, but the specific roles of most metals in this aspect are still unknown and require further research.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Zhong-Xuan Wang, Yao-Lin Li, Jia-Li Pu, Bao-Rong Zhang
Summary: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and the role of DNA damage and repair deficiency in its pathogenesis has been increasingly recognized. This review provides an overview of the current understanding of DNA damage and repair in PD, including the evidence and causes of DNA damage, the potential pathways linking DNA damage to neurotoxicity, and possible interventions targeting DNA damage and repair. Future research should focus on addressing key issues to further elucidate the role of DNA damage in PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Lin Wu, James R. Sowers, Yingmei Zhang, Jun Ren
Summary: Cardiovascular diseases (CVDs) are caused by abnormalities in the genomic, proteomic, and metabolomic aspects. Recent evidence has confirmed the presence of DNA damage in various CVDs. DNA damage triggers a cellular response called DNA damage response (DDR), which can be beneficial for cardiovascular function temporarily, but persistent activation of DDR promotes the onset and development of CVDs. Therefore, targeting DNA damage and DDR could potentially improve cardiovascular dysfunction and disease outcome.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cell Biology
Marta M. Morawska, Carlos G. Moreira, Varun R. Ginde, Philipp O. Valko, Tobias Weiss, Fabian Buechele, Lukas L. Imbach, Sophie Masneuf, Sedef Kollarik, Natalia Prymaczok, Juan A. Gerez, Roland Riek, Christian R. Baumann, Daniela Noain
Summary: Enhancing slow-wave sleep in murine models of Parkinson's disease reduces pathological alpha-synuclein accumulation and may improve disease progression through mechanisms such as promoting glymphatic clearance.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Geriatrics & Gerontology
Yao-Lin Li, Zhong-Xuan Wang, Chang-Zhou Ying, Bao-Rong Zhang, Jia-Li Pu
Summary: This article summarizes the evidence for nuclear DNA damage in Parkinson's disease (PD) and discusses the molecular mechanisms of nuclear DNA damage and repair in PD, particularly from the perspective of familial PD-related mutant genes, emphasizing the significance of DNA damage and repair as potential intervention targets for treating PD.
Review
Geriatrics & Gerontology
Zoltan Mari, Tiago A. Mestre
Summary: Parkinson's disease (PD) remains a progressive disease without a cure, despite the successful development of symptomatic treatments. The translation of disease-modifying interventions from preclinical models to clinical success has faced challenges in the past two decades. Lessons learned from high-quality clinical trials and advancements in PD molecular pathology can provide deeper insights into past failures and guide future research.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Clinical Neurology
John Stephen Middleton, Hanna Lynn Hovren, Nelson Kha, Manuel Joseph Medina, Karen Ruth MacLeod, Luis Concha-Marambio, Kendal Jay Jensen
Summary: Parkinson's disease (PD) can be misdiagnosed due to its clinical overlap with atypical parkinsonism. The a-Synuclein (aSyn) Seed Amplification Assay (SAA) has been reported as a potential diagnostic indicator for PD, but its use as a clinical laboratory test has not been validated. This study compares the accuracy of PD clinical diagnosis using the aSyn-SAA test with two different diagnostic inclusion criteria, showing a significant improvement when combined with confirmatory imaging.
JOURNAL OF NEUROLOGY
(2023)
Review
Neurosciences
Eunice Eun Seo Chang, Philip Wing-Lok Ho, Hui-Fang Liu, Shirley Yin-Yu Pang, Chi-Ting Leung, Yasine Malki, Zoe Yuen-Kiu Choi, David Boyer Ramsden, Shu-Leong Ho
Summary: Mutations in the LRRK2 gene are common causes of Parkinson's disease and suggest that LRRK2 could be a therapeutic target. LRRK2 mutant mice models show pathological similarities to early-stage Parkinson's disease, providing important insights into the mechanisms of the disease.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Biochemistry & Molecular Biology
Michele Salemi, Giovanna Marchese, Giuseppe Lanza, Filomena I. I. Cosentino, Maria Grazia Salluzzo, Francesca A. Schillaci, Giovanna Maria Ventola, Angela Cordella, Maria Ravo, Raffaele Ferri
Summary: Parkinson's disease (PD) is a neurodegenerative synucleinopathy with an unclear molecular pathomechanism. This study analyzed miRNAs on peripheral blood mononuclear cells from 30 participants to identify differentially expressed miRNAs in PD compared to healthy controls. The study also explored the pathways influenced by these miRNAs and their potential association with PD susceptibility. Several dysregulated miRNAs and their putative targets were identified, suggesting their potential as diagnostic markers and outcome measures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Isaac Perez-Segura, Alberto Santiago-Balmaseda, Luis Daniel Rodriguez-Hernandez, Adriana Morales-Martinez, Hilda Angelica Martinez-Becerril, Paola A. A. Martinez-Gomez, Karen M. M. Delgado-Minjares, Citlaltepetl Salinas-Lara, Irma A. A. Martinez-Davila, Magdalena Guerra-Crespo, Francisca Perez-Severiano, Luis O. O. Soto-Rojas
Summary: Parkinson's disease (PD) is characterized by the misfolding and propagation of alpha-synuclein protein, leading to neurodegeneration. Peroxisome proliferator-activated receptor (PPAR) agonists have shown neuroprotective effects in PD, but their potential anti-alpha-synucleinopathy effects are still unclear. This article analyzes the therapeutic effects of PPARs, specifically PPAR gamma, in PD animal models and clinical trials, and suggests potential mechanisms against alpha-synucleinopathy. Understanding the neuroprotective mechanisms of PPARs will improve the development of disease-modifying drugs for PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Aicha Sassi, Maxime Fredon, Alexia K. Cotte, Camille Fuselier, Christophe Schneider, Laurent Martiny, David Monchaud, Leila Chekir-Ghedira, Virginie Aires, Dominique Delmas
Summary: Despite progress in treatments, melanoma incidence and mortality have increased. Chrysin, a natural polyphenol, shows potential as a therapeutic strategy due to its modulation of tumorigenesis and resistance mechanisms. This study reveals a link between chrysin-induced antitumoral effects, DNA damage pathway activation, and reduced angiogenesis in melanoma cells. The disruption of key protein actors in tumor growth by chrysin suggests its potential as a new therapeutic strategy in melanoma treatment.
Review
Neurosciences
Claudia P. Gonzalez-Hunt, Laurie H. Sanders
Summary: Parkinson's disease is a common movement neurodegenerative disorder, but the understanding of its pathogenesis has not yet led to effective therapies. Further research is needed to explore the multifactorial etiology of PD.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Review
Clinical Neurology
Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida, Gabriel Ginani Ferreira, Andrezza Paula Brito Silva, Pedro Renato de Paula Brandao, Wolfgang H. Oertel, Carlos H. Schenck, Raimundo Nonato Delgado Rodrigues
Summary: The flow of gene expression is a tightly controlled cell process, with microRNAs playing a crucial role in maintaining healthy cell physiology. Aberrant expressions of microRNAs are associated with Parkinson's disease pathogenesis, while REM-sleep behavior disorder may serve as a valuable phenotype for disease prediction.
Article
Clinical Neurology
Timo Siepmann, Martin Arndt, Annahita Sedghi, Szabolcs Szatmari Jr, Tamas Horvath, Annamaria Takats, Daniel Bereczki, Mats Leif Moskopp, Sylvia Buchmann, Cornelia Skowronek, Wagner Zago, Warunya Woranush, Razvan Lapusca, Marie Luise H. Weidemann, Christopher Gibbons, Roy Freeman, Heinz Reichmann, Volker Puetz, Kristian Barlinn, Alexandra Pinter, Ben Min-Woo Illigens
Summary: This study characterized autonomic pilomotor and sudomotor skin function in early Parkinson's disease (PD) longitudinally. The results showed that pilomotor function and sympathetic skin response (SSR) were impaired in PD, indicating sympathetic pathophysiology. However, cholinergic sudomotor function and parasympathetic neurocardiac function remained unchanged. This finding suggests that a pilomotor axon-reflex test may be useful for monitoring PD-related pathology.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Alysa Kasen, Christina Houck, Amanda R. Burmeister, Qiong Sha, Lena Brundin, Patrik Brundin
Summary: Alpha-synuclein plays multiple roles in neurons and is involved in the pathogenesis of synucleinopathies. Recent evidence suggests its potential involvement in the immune response, and under certain conditions, its aggregation may trigger neurodegenerative diseases.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Chiara Milanese, Sylvia Gabriels, Sander Barnhoorn, Silvia Cerri, Ayse Ulusoy, S. V. Gornati, Daniel F. Wallace, Fabio Blandini, Donato A. Di Monte, V. Nathan Subramaniam, Pier G. Mastroberardino
Summary: Alterations in iron metabolism and accumulation are associated with the pathogenesis of Parkinson's disease. Targeting TfR2 pathway can be a potential therapeutic strategy to inhibit iron overload and PD progression, with neuroprotective effects showing sexual dimorphism.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Silvia Cerri, Cristina Ghezzi, Gerardo Ongari, Stefania Croce, Micol Avenali, Roberta Zangaglia, Donato A. Di Monte, Enza Maria Valente, Fabio Blandini
Summary: This study found that GCase deficiency promotes the release of EVs, leading to increased levels of phosphorylated alpha-syn inside fibroblasts from PD patients. This suggests that dysregulation of EV trafficking and mishandling of alpha-synuclein may play a role in GBA-associated PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Alessandro Petese, Valentina Cesaroni, Silvia Cerri, Fabio Blandini
Summary: Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by lysosomal dysfunction and aggregation of alpha-synuclein protein. Modulating lysosomal pathways may offer a novel approach for PD treatment.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2022)
Review
Biochemistry & Molecular Biology
Paola Imbriani, Giuseppe Sciamanna, Ilham El Atiallah, Silvia Cerri, Ellen J. Hess, Antonio Pisani
Summary: Alcohol consumption affects motor behavior and control, but the therapeutic mechanism for movement disorders like myoclonus-dystonia remains unclear, with few systematic trials on GABA drugs mimicking alcohol effects. This survey aims to summarize the impact of EtOH on striatal function and provide a mechanistic explanation for alcohol-responsive movement disorders, suggesting potential drug repositioning based on different hypotheses.
Article
Cell Biology
Marianna Tolve, Ayse Ulusoy, Nikolaos Patikas, K. Ushna S. Islam, Gabriela O. Bodea, Ece Oeztuerk, Bianca Broske, Astrid Mentani, Antonia Wagener, Karen M. J. van Loo, Stefan Britsch, Pengtao Liu, Walid T. Khaled, Emmanouil Metzakopian, Stephan L. Baader, Donato A. Di Monte, Sandra Blaess
Summary: The transcription factor BCL11A is expressed in subsets of murine and human dopamine neurons, forming specific subcircuits within the dopamine system. These Bcl11a-expressing neurons are vulnerable to neurodegeneration, as inactivation of Bcl11a increases susceptibility and results in motor behavior deficits. BCL11A is crucial for establishing and maintaining the physiological characteristics of dopamine neuron subpopulations.
Article
Physiology
Riccardo Cremascoli, Davide Sparasci, Gianluca Giusti, Stefania Cattaldo, Elisa Prina, Fausto Roveta, Francesco Bruno, Cristina Ghezzi, Silvia Cerri, Marta Picascia, Sara Bernini, Elena Sinforiani, Michele Terzaghi, Lorenzo Priano, Alessandro Mauro, Raffaele Manni
Summary: This study investigates the effects of light therapy on sleep quality, mood, and cognition in patients with mild/moderate Alzheimer's disease. It is shown that light therapy tailored to the individual's circadian phase can induce a circadian phase shift, improve subjective sleep quality and cognitive performance, and shorten the time between dim light melatonin onset and falling asleep.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Clinical Neurology
Celine Galvagnion, Frederik Ravnkilde Marlet, Silvia Cerri, Anthony H. Schapira, Fabio Blandini, Donato A. Di Monte
Summary: This study found that mutations of the glucocerebrosidase 1 (GBA) gene, a prevalent risk factor for Parkinson's disease, led to altered lipid membrane composition in Parkinson fibroblasts. The altered lipid profile featured increased levels of sphingolipids and shorter-chain sphingolipid molecules. The extent of this alteration was correlated with the reduction of fibroblast glucocerebrosidase activity and accelerated alpha-synuclein aggregation. Treatment with a small molecule chaperone, ambroxol, restored the lipid profile and reversed the pro-aggregation effect. These findings suggest that the GBA mutation and consequent loss of enzymatic activity are associated with a distinct membrane lipid profile, which may increase the risk for alpha-synuclein aggregate pathology.
Article
Clinical Neurology
Giulia Ponterio, Gaia Faustini, Ilham El Atiallah, Giuseppe Sciamanna, Maria Meringolo, Annalisa Tassone, Paola Imbriani, Silvia Cerri, Giuseppina Martella, Paola Bonsi, Arianna Bellucci, Antonio Pisani
Summary: This study reveals the relationship between TA and alpha-Syn and demonstrates that alterations in alpha-Syn and SNAREs characterize the synaptic dysfunction underlying DYT1 dystonia.
MOVEMENT DISORDERS
(2022)
Article
Neurosciences
Iris Lindberg, Zhan Shu, Hoa Lam, Michael Helwig, Nur Yucer, Alexander Laperle, Clive N. Svendsen, Donato A. Di Monte, Nigel T. Maidment
Summary: The study demonstrates that proSAAS chaperone is effective in reducing motor deficits and neuronal damage caused by aSyn in Parkinson's disease, and can block the transsynaptic spread of aSyn.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Multidisciplinary Sciences
Michael Helwig, Ayse Ulusoy, Angela Rollar, Sinead A. O'Sullivan, Shirley S. L. Lee, Helia Aboutalebi, Rita Pinto-Costa, Benjamin Jevans, Michael Klinkenberg, Donato A. Di Monte
Summary: This study revealed the influence of neuronal activity on the transfer of alpha-synuclein, with hyperactivity enhancing protein transfer and hypoactivity attenuating it. High neuronal activity exacerbated oxidative and nitrative reactions, leading to nitration of alpha-synuclein and increased protein aggregation. Mitochondria were identified as key targets and potential sources of reactive oxygen and nitrogen species within hyperactive neurons.
Article
Neurosciences
Claudio Giuliano, Silvia Cerri, Valentina Cesaroni, Fabio Blandini
Summary: Parkinson's disease (PD) is a degenerative disorder characterized by the loss of dopaminergic neurons in the brain. The search for disease-modifying therapies for PD has been challenging due to the heterogeneity of patients and the lack of approved drugs. Stratification of PD patients based on their expected response to targeted drugs and biochemical phenotyping is a promising approach for clinical trials. Various studies have proposed biochemical characterizations of PD cohorts using different biological samples, with a focus on biomarkers such as α-synuclein and neurofilament light chain. Although still in its early stages, deep phenotyping of PD patients has the potential to identify homogeneous subgroups for tailored therapies and improve therapeutic outcomes.
Article
Cell Biology
Michael Klinkenberg, Michael Helwig, Rita Pinto-Costa, Angela Rollar, Raffaella Rusconi, Donato A. Di Monte, Ayse Ulusoy
Summary: Neuron-to-neuron transfer of pathogenic alpha-synuclein is likely relevant to Parkinson's disease development, and the spreading ability of alpha-synuclein can be reproduced by injecting AAV vectors encoding for alpha-synuclein into the mouse vagus nerve. This study investigated whether other proteins share this spreading ability. Results showed that beta-synuclein, but not VAMP2 or SNAP25, can spread to more frontal brain regions, and protein aggregation may be involved in this spreading mechanism.
Article
Biochemistry & Molecular Biology
Silvia Pisani, Deborah Di Martino, Silvia Cerri, Ida Genta, Rossella Dorati, Giulia Bertino, Marco Benazzo, Bice Conti
Summary: In this study, four different active encapsulation methods were compared for loading a model protein into liposomes. Electroporation yielded the highest encapsulation efficiency, but led to a significant increase in liposome size. Freeze-thawing was an effective method, allowing for high encapsulation efficiency while maintaining suitable size. Charged liposomes showed slower in vitro release and good cytocompatibility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Valentina Cesaroni, Fabio Blandini, Silvia Cerri
Summary: LIDs are supported by complex molecular and neurobiological mechanisms that are still being studied today. This complexity suggests the need of developing personalized pharmacological approach to obtain an effective amelioration of LID condition and improve the quality of life of PD patients.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)