Unlabelled: This review describes recent developments in the search for effective therapeutic agents that target redox homeostasis in neurodegenerative disease. The disruption to thiol redox homeostasis in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis is discussed, together with the experimental strategies that are aimed at preventing, or at least minimizing, oxidative damage in these diseases. Particular attention is given to the potential of increasing antioxidant capacity by targeting the Nrf2 pathway, the development of inhibitors of NADPH oxidases that are likely candidates for clinical use, together with strategies to reduce nitrosative stress and mitochondrial dysfunction. We describe the shortcomings of compounds that hinder their progression to the clinic and evaluate likely avenues for future research.
Linked Articles: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.
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http://dx.doi.org/10.1111/bph.13551 | DOI Listing |
Eur J Neurosci
March 2025
Parkinson's Disease and Movement Disorders Clinic, Bangalore, India.
The release of synaptic vesicles (SVs) at the synaptic junction is a complex process involving various specialized proteins that work in unison. Among these, Bassoon has emerged as a significant protein, particularly noted for its association with various neurological and aging-related diseases. Due to its structural and functional roles, Bassoon has become a focus of recent research, especially in understanding its implications in neurodegenerative and psychiatric disorders.
View Article and Find Full Text PDFJ Am Chem Soc
March 2025
Institute of Biological Chemistry, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 115, Taiwan.
In this study, the role of phosphorylation in the liquid-liquid phase separation (LLPS) of tau, the underlying driving forces, and the potential implications of this separation on protein conformation and subsequent protein aggregation were investigated. We compared in vivo-produced phosphorylated tau (p-tau) and nonphosphorylated tau under different coacervation conditions without adding crowding agents. Our findings revealed that spontaneous phase separation occurs exclusively in p-tau, triggered by a temperature shift from 4 °C to room temperature, and is driven by electrostatic and hydrophobic interactions.
View Article and Find Full Text PDFJ Am Coll Cardiol
March 2025
National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom.
Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed chronic disease associated with progressive heart failure that results in impaired quality of life, repeated hospitalizations, and premature death. Acoramidis is a selective, oral transthyretin stabilizer recently approved by the U.S.
View Article and Find Full Text PDFHandb Clin Neurol
March 2025
Department of Psychology, University of Campania 'Luigi Vanvitelli', Caserta, Italy. Electronic address:
This chapter deals with the unique human abilities of using tools, imitating others' gestures, drawing, and building complex items. Herein, after a brief overview of clinical manifestations and assessment of disorders of tool use and imitation (upper limb apraxia) and of the impairments in drawing and assembling multipart objects (constructional apraxia), brain asymmetries are discussed mainly starting from the neuropsychologic studies on patients with focal brain lesions, although both upper limb apraxia and constructional apraxia are often observed during the course of neurodegenerative diseases. Although no room is allowed here for a full discussion of brain-behavior relationships, relevant functional neuroimaging findings in healthy individuals are considered.
View Article and Find Full Text PDFHandb Clin Neurol
March 2025
University School for Advanced Studies (IUSS-Pavia), Pavia, Italy; Dementia Research Center, IRCCS Mondino Foundation, Pavia, Italy. Electronic address:
Hemispheric asymmetry in pathologic involvement is frequently observed in neurodegenerative disorders (NDD) and is responsible for differences in cognitive and motor clinical manifestations in individual patients. While asymmetry is modest in typical Alzheimer disease (AD), atypical AD presentations with prominent language impairment [logopenic/phonologic variant of primary progressive aphasia (L/Phv-PPA)] are associated with prevalent involvement of the language-dominant hemisphere. Similarly, in the frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum, the semantic (Sv) and nonfluent/agrammatic (Nf/Av) variants of PPA are due to asymmetric pathology involving the language-dominant hemisphere.
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