Argyrophilic Grain Disease Clinically Presenting as Progressive Supranuclear Palsy with Progressive Gait Freezing DOI
Renpei Sengoku, Akira Arakawa, Tomoyasu Matsubara

et al.

Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract Background Argyrophilic grain disease (AGD) is a four‐repeat tauopathy characterized by the accumulation of argyrophilic grains. Its primary clinical manifestation late‐onset amnestic dementia. While extension grains to substantia nigra may be related its potential association with parkinsonism, biochemical analyses are lacking. Objectives To elucidate extent AGD midbrain, including nigra, using histopathological examination and analysis in pathologically proven case presenting parkinsonism cognitive impairment. Methods We describe patient suggestive progressive supranuclear palsy. Neuropathological investigations were performed. Results Neurological an 80‐year‐old man 6‐year history gait disturbance revealed freezing, postural instability, bradykinesia, The was diagnosed palsy freezing. Five years later, reported falling backward repeatedly, became wheelchair‐bound, died pneumonia. Macroscopic observations marked amygdala atrophy. Microscopic findings limbic system, compatible Saito stage III, as well midbrain tegmentum. Western blotting showed AGD‐specific band pattern, immunoelectron microscopy tau filament abnormally phosphorylated both nucleus accumbens midbrain. Conclusions This report further confirmed that presents commensurate pathology extending Therefore, should considered differential diagnosis cases impairment older population.

Language: Английский

Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease DOI Creative Commons
Minghui Wang, Hu Zhang, Jiling Liang

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: March 19, 2023

Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disease, with the characteristics of neurofibrillary tangle (NFT) and senile plaque (SP) formation. Although great progresses have been made in clinical trials based on relevant hypotheses, these studies are also accompanied by emergence toxic side effects, it an urgent task to explore underlying mechanisms for benefits prevent treat AD. Herein, animal experiments few trials, neuroinflammation AD characterized long-term activation pro-inflammatory microglia NOD-, LRR- pyrin domain-containing protein 3 (NLRP3) inflammasomes. Damaged signals from periphery within brain continuously activate microglia, thus resulting constant source inflammatory responses. The response exacerbates endoplasmic reticulum oxidative stress which triggers microglia-dependent immune responses, ultimately leading occurrence deterioration In this review, we systematically summarized sorted out that exercise ameliorates directly indirectly regulating central nervous system promoting hippocampal neurogenesis provide new direction exploring activity

Language: Английский

Citations

85

TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP DOI Creative Commons
Diana Arseni, Renren Chen,

Alexey G. Murzin

et al.

Nature, Journal Year: 2023, Volume and Issue: 620(7975), P. 898 - 903

Published: Aug. 2, 2023

Abstract The abnormal assembly of TAR DNA-binding protein 43 (TDP-43) in neuronal and glial cells characterizes nearly all cases amyotrophic lateral sclerosis (ALS) around half frontotemporal lobar degeneration (FTLD) 1,2 . A causal role for TDP-43 neurodegeneration is evidenced by dominantly inherited missense mutations TARDBP , the gene encoding TDP-43, that promote give rise to ALS FTLD 3–7 At least four types (A–D) with pathology (FTLD-TDP) are defined distinct brain distributions assembled associated different clinical presentations dementia 8 We previously showed, using cryo-electron microscopy, assembles into amyloid filaments type B FTLD-TDP 9 However, structures without remained unknown. Here we report microscopy from brains three individuals most common FTLD-TDP, A. formed a new fold was same across individuals, indicating this may characterize FTLD-TDP. resembles chevron badge unlike double-spiral-shaped establishing filament folds neurodegenerative conditions. structures, combination mass spectrometry, led identification two post-translational modifications citrullination monomethylation R293, indicate they facilitate formation observed structural variation individual filaments. will guide mechanistic studies assembly, as well development diagnostic therapeutic compounds proteinopathies.

Language: Английский

Citations

73

A structural basis for prion strain diversity DOI Creative Commons
Szymon W. Manka,

Adam Wenborn,

Jemma Betts

et al.

Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 19(5), P. 607 - 613

Published: Jan. 16, 2023

Abstract Recent cryogenic electron microscopy (cryo-EM) studies of infectious, ex vivo, prion fibrils from hamster 263K and mouse RML strains revealed a similar, parallel in-register intermolecular β-sheet (PIRIBS) amyloid architecture. Rungs the are composed individual protein (PrP) monomers that fold to create distinct N-terminal C-terminal lobes. However, disparity in hamster/mouse PrP sequence precludes understanding how divergent emerge an identical substrate. In this study, we determined near-atomic resolution cryo-EM structure vivo ME7 strain compared with fibril structure. This structural comparison two biologically mouse-adapted suggests defined folding subdomains rungs way which they interrelated, providing definition intra-species strain-specific conformations.

Language: Английский

Citations

57

Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP Type C DOI Creative Commons
Diana Arseni, Takashi Nonaka, Max Jacobsen

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8034), P. 662 - 668

Published: Sept. 11, 2024

Language: Английский

Citations

27

Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases DOI
Sukriti Nag, Julie A. Schneider

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(9), P. 525 - 541

Published: Aug. 10, 2023

Language: Английский

Citations

26

The Misfolding Mystery: α-syn and the Pathogenesis of Parkinson's Disease DOI

Samir Negi,

Navneet Khurana,

Navneet Duggal

et al.

Neurochemistry International, Journal Year: 2024, Volume and Issue: 177, P. 105760 - 105760

Published: May 7, 2024

Language: Английский

Citations

14

Sodium Dodecyl Sulfate Analogs as a Potential Molecular Biology Reagent DOI Creative Commons
Tsutomu Arakawa, Takako Niikura,

Yoshiko Kita

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(1), P. 621 - 633

Published: Jan. 9, 2024

In this study, we review the properties of three anionic detergents, sodium dodecyl sulfate (SDS), Sarkosyl, and lauroylglutamate (SLG), as they play a critical role in molecular biology research. SDS is widely used electrophoresis cell lysis for proteomics. Sarkosyl and, more frequently, are characterization neuropathological protein fibrils solubilization proteins. Many amyloid resistant to or different degrees thus, can be readily isolated from detergent-sensitive SLG milder than above two detergents has been refolding proteins inclusion bodies. Here, show that both have refolding, effects on native structure weaker SLG, dissociates We propose may effective functional proteomics due no binding

Language: Английский

Citations

11

Nature's toolbox against tau aggregation: An updated review of current research DOI
Sumaiya Khan, Md. Imtaiyaz Hassan, Mohammad Shahid

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101924 - 101924

Published: March 31, 2023

Language: Английский

Citations

23

α-Synuclein Conformational Strains as Drivers of Phenotypic Heterogeneity in Neurodegenerative Diseases DOI Open Access
Raphaella W. L. So, Joel C. Watts

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 435(12), P. 168011 - 168011

Published: Feb. 14, 2023

Language: Английский

Citations

19

The Role of the Glymphatic Clearance System in the Mechanisms of the Interactions of the Sleep–Waking Cycle and the Development of Neurodegenerative Processes DOI
Igor Shirolapov, Alexander Zakharov, Daria Smirnova

et al.

Neuroscience and Behavioral Physiology, Journal Year: 2024, Volume and Issue: 54(2), P. 199 - 204

Published: Feb. 1, 2024

Language: Английский

Citations

8