Aoffa-Synuclein, a presynaptic nerve terminal protein, may be an important component of Lewy bodies in Parkinson's disease, dementia with Lewy bodies, and other neurodegenerative diseases. Additionally, recent genetic studies based on linkage analysis and cosegregation of A53T and A30P missense mutations demonstrated that the alpha-synuclein gene may be responsible for the development of at least some cases of familial Parkinson's disease. Despite intense interest in the members of the synuclein family, their function(s) and exact role in the diseases remained unknown. Here we describe a new member of the synuclein family, which we term synoretin, and show that it is expressed in different retinal cells, as well as in the brain, and it may affect the regulation of signal transduction through activation of the Elk1 pathway.
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http://dx.doi.org/10.1006/mcne.1999.0735 | DOI Listing |
Sci Adv
January 2025
New Cornerstone Science Laboratory, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
Deep brain stimulation technology enables the neural modulation with precise spatial control but requires permanent implantation of conduits. Here, we describe a photothermal wireless deep brain stimulation nanosystem capable of eliminating α-synuclein aggregates and restoring degenerated dopamine neurons in the substantia nigra to treat Parkinson's disease. This nanosystem (ATB NPs) consists of gold nanoshell, an antibody against the heat-sensitive transient receptor potential vanilloid family member 1 (TRPV1), and β-synuclein (β-syn) peptides with a near infrared-responsive linker.
View Article and Find Full Text PDFParkinsonism Relat Disord
December 2024
Department of Translational Neuroscience and the Muhammad Ali Parkinson Center, Barrow Neurological Institute, Phoenix, AZ, USA.
The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ("seed") to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined.
View Article and Find Full Text PDFAutophagy
January 2025
Laboratory of Molecular Neuropathology, Department of Pharmacology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
The aggregation and transmission of SNCA/α-synuclein (synuclein, alpha) is a hallmark pathology of Parkinson disease (PD). PLK2 (polo like kinase 2) is an evolutionarily conserved serine/threonine kinase that is more abundant in the brains of all family members, is highly expressed in PD, and is linked to SNCA deposition. However, in addition to its role in phosphorylating SNCA, the role of PLK2 in PD and the mechanisms involved in triggering neurodegeneration remain unclear.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Mutations in leucine-rich repeat kinase 2 () are the most common cause of familial and sporadic Parkinson's disease (PD). While the clinical features of -PD patients resemble those of typical PD, there are significant differences in the pathological findings. The pathological hallmark of definite PD is the presence of α-synuclein (αSYN)-positive Lewy-related pathology; however, approximately half of -PD cases do not have Lewy-related pathology.
View Article and Find Full Text PDFBioorg Med Chem
February 2025
Tsukuba Research Center, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
NLRP3 inflammasome inhibitor is a highly attractive drug target for the treatment of various inflammatory diseases. Here, we report the discovery of pyridazine derivatives as a new class of scaffold for NLRP3 inflammasome inhibitors. We optimized HTS hit 2a to improve both in vitro IL-1β inhibitory activity and the mean photo effect (MPE) value in the in vitro 3T3 neutral red uptake (NRU) phototoxicity test.
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