We investigated a large family with levodopa-responsive, Lewy body parkinsonism in which the disease segregates as an apparent autosomal dominant trait. After performing a genome screen, we identified a chromosome 4p haplotype that segregates with the disease. However, this haplotype also occurs in individuals in the pedigree who do not have clinical Lewy body parkinsonism but rather suffer from postural tremor, consistent with essential tremor. These data demonstrate a new locus for Lewy body parkinsonism and suggest that in some circumstances postural tremor can be an alternative phenotype of the samepathogenic mutation as Lewy body parkinsonism.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1093/hmg/8.1.81 | DOI Listing |
CNS Neurol Disord Drug Targets
January 2025
Department of Biotechnology, National Institute of Technology, Raipur, 492001, India.
Parkinson's disease (PD) is a neurodegenerative disorder that results from the progressive loss of neurons in the brain followed by symptoms such as slowness and rigidity in movement, sleep disorders, dementia and many more. The different mechanisms due to which the neuronal degeneration occurs have been discussed, such as mutation in PD related genes, formation of Lewy bodies, oxidation of dopamine. This review discusses current surgical treatment and gene therapies with novel developments proposed for PD.
View Article and Find Full Text PDFCommun Biol
January 2025
Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA.
Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs.
View Article and Find Full Text PDFNPJ Parkinsons Dis
January 2025
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20852, USA.
ΑBSTRACT: In Parkinson's disease (PD), Lewy pathology deposits in the cerebral cortex, but how the pathology disrupts cortical circuit integrity and function remains poorly understood. To begin to address this question, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. We reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern.
View Article and Find Full Text PDFExp Neurobiol
December 2024
Dementia Brain Bank, Seoul National University Hospital, Seoul 03080, Korea.
This paper introduces the current status of Seoul National University Hospital Dementia Brain Bank (SNUH-DBB), focusing on the concordance rate between clinical diagnoses and postmortem neuropathological diagnoses. We detail SNUH-DBB operations, including protocols for specimen handling, induced pluripotent stem cells (iPSC) and cerebral organoids establishment from postmortem dural fibroblasts, and adult neural progenitor cell cultures. We assessed clinical-neuropathological diagnostic concordance rate.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, United States of America. Electronic address:
Aggregation of alpha-synuclein (αsyn) plays an integral role in Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). 14-3-3θ is a highly expressed brain protein with chaperone-like activity that regulates αsyn folding. 14-3-3θ overexpression reduces αsyn aggregation, transmission between cells, and neuronal loss, while 14-3-3 inhibition promotes αsyn pathology.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!