Objective: This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP.
Material And Methods: We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis.
Results: The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs.
Conclusion: These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.
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http://dx.doi.org/10.1002/acn3.285 | DOI Listing |
J Ethnopharmacol
January 2025
Heilongjiang University of Chinese Medicine, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education Heilongjiang Touyan Innovation Team Program, Harbin 150040, People's Republic of China. Electronic address:
Ethnopharmacological Relevance: Schisandra chinensis (Turcz.) Baill (S. chinensis), first recorded in Shennong's Classic of the Materia Medica, is described as a "top grade medicine".
View Article and Find Full Text PDFEur J Med Chem
January 2025
Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China. Electronic address:
The development of potent glycogen synthase kinase-3β (GSK-3β) inhibitor has been increasingly recognized as the candidate treatment against the multifactorial pathogenic mechanism of Alzheimer's disease (AD). This study prepared various new pyrrolo[2,3-b]pyridine derivatives, evaluated the anti-AD activities and detected the security based on the structure-guided rational design. Our results indicated that many pyrrolo[2,3-b]pyridine derivatives had strong GSK-3β inhibitory activities, particularly compounds 41, 46 and 54, with the half maximal inhibitory concentrations (IC) of 0.
View Article and Find Full Text PDFChemistryOpen
January 2025
Department of Chemistry, Faculty of Sciences, University of Guilan, Rasht, 4193833697, Iran.
The inhibition of acetylcholinesterase (AChE), an enzyme responsible for the inactivation and decrease in acetylcholine in the cholinergic pathway, has been considered an attractive target for small-molecule drug discovery in Alzheimer's disease (AD) therapy. In the present study, a series of TZD derivatives were designed, synthesized, and studied for drug likeness, blood-brain barrier (BBB) permeability, and adsorption, distribution, metabolism, excretion, and toxicity (ADMET). Additionally, docking studies of the designed compounds were performed on AChE.
View Article and Find Full Text PDFEMBO Mol Med
January 2025
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
In Alzheimer's disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau determined in the cerebrospinal fluid (CSF).
View Article and Find Full Text PDFJ Neuropsychiatry Clin Neurosci
January 2025
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
Objective: Cognitive impairment is a common nonmotor symptom among individuals with Parkinson's disease (PD). Although cognitive impairment generally develops progressively, individuals with PD-associated mild cognitive impairment (PD-MCI) may revert to being cognitively normal (CN), which is referred to as PD-MCI reversion. Previous studies are inconsistent in whether PD-MCI reverters are at greater risk for PD-MCI recurrence relative to CN individuals.
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