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Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.
Mol Neurodegener
January 2025
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
α-Synucleinopathies constitute a spectrum of neurodegenerative disorders, including Parkinson's disease (PD), Lewy body dementia (LBD), Multiple System Atrophy (MSA), and Alzheimer's disease concurrent with LBD (AD-LBD). These disorders are unified by a pathological hallmark: aberrant misfolding and accumulation of α-synuclein (α-syn). This review delves into the pivotal role of α-syn, the key agent in α-synucleinopathy pathophysiology, and provides a survey of potential therapeutics that target cell-to-cell spread of pathologic α-syn.
View Article and Find Full Text PDF[Language impairment in Lewy body disease: A systematic review].
Geriatr Psychol Neuropsychiatr Vieil
September 2024
Unité PsyNcog, ULG, Liège, Belgique, Centre mémoire ressources et recherche, CHRU Tours, France.
Distinct subcellular localization of tau and alpha-synuclein in lewy body disease.
Acta Neuropathol Commun
January 2025
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of tau's phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates.
View Article and Find Full Text PDFIs Charles Bonnet Syndrome a Harbinger of Neurocognitive Disorder With Lewy Bodies? A Clinical Conundrum.
J Psychiatr Pract
January 2025
Department of Psychiatry, Centre for Addiction Medicine, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.
Charles Bonnet syndrome (CBS) is a clinical condition in which patients with visual impairment experience visual hallucinations (VH) in the presence of clear consciousness. It typically occurs in elderly people and confuses clinicians with multiple differential diagnoses due to VH, which can be present in a variety of clinical conditions ranging from psychosis to neurocognitive disorders (eg, neurocognitive disorder with Lewy bodies). In the latter, the concomitant presence of cognitive decline and parkinsonism aids the diagnosis.
View Article and Find Full Text PDFBidirectional Mendelian Randomization Analysis of the Association Between Mitochondrial Proteins and Neurodegenerative Diseases.
Brain Behav
January 2025
Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Background: Neurodegenerative diseases involve progressive neuronal dysfunction and cognitive decline, posing substantial global challenges. Although the precise causes remain unclear, several studies highlight the role of protein metabolism abnormalities in disease development. This study investigates the causal links between variations in mitochondrial protein genes and neurodegenerative diseases, aiming to elucidate their potential contributions to disease progression and identify novel therapeutic strategies.
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