Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5494 - 5509
Published: Jan. 10, 2024
Language: Английский
Redox Biology, Journal Year: 2023, Volume and Issue: 61, P. 102637 - 102637
Published: Feb. 14, 2023
Alzheimer's disease is a neurodegenerative disorder characterized by decline in cognitive function. The β-amyloid (Aβ) hypothesis suggests that Aβ peptides can spontaneously aggregate into β-fragment-containing oligomers and protofibrils, this activation of the amyloid pathway alters Ca2+ signaling neurons, leading to neurotoxicity thus apoptosis neuronal cells. In our study, blood-brain barrier crossing flavonol glycoside hyperoside was identified with anti-Aβ aggregation, BACE inhibitory, neuroprotective effect cellular or APP/PSEN1 double transgenic mice model. While pharmacokinetic data confirmed intranasal administration resulted higher bio-availability brain, further vivo studies revealed it improved motor deficit, spatial memory learning ability reducing level plaques GFAP cortex hippocampus. Bioinformatics, computational docking vitro assay results suggested bind interacted ryanodine receptors, then regulated via endoplasmic reticulum-mitochondrial calcium (Ca2+) pathway. Consistently, increased Bcl2, decreased Bax cyto-c protein levels, ameliorated cell death both By regulating Aβ-induced regulation on cascade mitochondrial membrane potential, study may work as potential therapeutic agent preventive remedy for disease.
Language: Английский
Citations
23
Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106047 - 106047
Published: Feb. 23, 2023
Brain
functional
connectivity
in
dementia
has
been
assessed
with
dissimilar
EEG
metrics
and
estimation
procedures,
thereby
increasing
results'
heterogeneity.
In
this
scenario,
joint
analyses
integrating
information
from
different
may
allow
for
a
more
comprehensive
characterization
of
brain
interactions
subtypes.
To
test
hypothesis,
resting-state
electroencephalogram
(rsEEG)
was
recorded
individuals
Alzheimer's
Disease
(AD),
behavioral
variant
frontotemporal
(bvFTD),
healthy
controls
(HCs).
Whole-brain
estimated
the
source
space
using
101
types
connectivity,
capturing
linear
nonlinear
both
time
frequency-domains.
Multivariate
machine
learning
progressive
feature
elimination
run
to
discriminate
AD
HCs,
bvFTD
based
on
i)
frequency
bands,
ii)
complementary
frequency-domain
(e.g.,
instantaneous,
lagged,
total
connectivity),
iii)
time-domain
linearity
assumption
Pearson
correlation
coefficient
mutual
information).
<10%
all
possible
connections
were
responsible
differences
between
patients
controls,
atypical
never
captured
by
>1/4
measures.
Joint
revealed
patterns
hypoconnectivity
(patients
Language: Английский
Citations
23
Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)
Published: Jan. 11, 2025
Language: Английский
Citations
1
Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 28
Published: Jan. 21, 2025
Genetic load influences the therapeutic response to conventional drugs in Alzheimer's disease (AD). Pharmacogenetics (PGx) is best option reduce drug-drug interactions and adverse drug reactions patients undergoing polypharmacy regimens. However, there are important limitations that make it difficult incorporate pharmacogenetics into routine clinical practice. This article analyzes pharmacogenetic apparatus made up of pathogenic, mechanistic, metabolic, transporter, pleiotropic genes responsible for efficacy safety pharmacological treatment, impact genetic on outcome multifactorial treatments, practical aspects effective use PGx. Over 120 closely associated with AD. There an accumulation cerebrovascular (CVn) neurodegenerative (ADn) APOE-4 carriers accumulate more deleterious related other CVn ADn genes, develop earlier, at a biological disadvantage compared non-carriers. CYP2D6-PMs worst responders anti-dementia drugs. Some hinder implementation PGx practice, including lack information many drugs, low number screening protocols, educational deficiencies medical community regarding genomic medicine.
Language: Английский
Citations
1
Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123142 - 123142
Published: Jan. 1, 2025
Language: Английский
Citations
1
Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)
Published: March 27, 2025
Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play central role. These immune cells undergo reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, HIF-1α orchestrating these processes. Microglial metabolism adapts environmental stimuli, shifting oxidative phosphorylation glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts an energy sensor, coordinating lipid glucose metabolism. TREM2 APOE regulate microglial homeostasis, influencing Aβ clearance responses. LPL ABCA7, both associated AD risk, modulate processing cholesterol transport, linking neurodegeneration. PPARG further supports by regulating inflammatory Amino acid also contributes function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked pathology. Additionally, glucose-6-phosphate dehydrogenase regulates pentose phosphate maintaining redox balance activation. Dysregulated metabolism, influenced genetic variants APOE4, impair responses exacerbate progression. Recent findings highlight interplay regulators like REV-ERBα, which modulates inflammation, Syk, influences clearance. insights offer promising therapeutic targets, including strategies aimed at modulation, could restore function depending on stage. By integrating metabolic, immune, factors, this review underscores importance of immunometabolism AD. Targeting pathways provide novel for mitigating restoring function, ultimately paving way innovative treatments neurodegenerative diseases.
Language: Английский
Citations
1
Information Processing & Management, Journal Year: 2023, Volume and Issue: 60(4), P. 103362 - 103362
Published: April 1, 2023
Language: Английский
Citations
22
Dementia and Geriatric Cognitive Disorders, Journal Year: 2023, Volume and Issue: 52(2), P. 47 - 73
Published: Jan. 1, 2023
Introduction: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer’s disease (AD). However, there is absence of visual overviews assess the published literature systematically. Methods: In this review, bibliometric approach was used estimate searched data on stem cell research in AD from 2004 2022, we also utilized CiteSpace VOSviewer software evaluate contributions co-occurrence relationships different countries/regions, institutes, journals, authors as well discover hot spots encouraging future trends field. Results: From a total 3,428 publications were retrieved. The number citations increased dramatically last nearly 20 years, especially since 2016. North America Asia top 2 highest output regions. leading country terms access collaborative networks USA. Centrality analysis revealed that UCL (0.05) at core network. Journal Disease (n = 102, 2.98%) most productive academic journal. analyses keyword burst detection indicated exosomes, risk factors, drug delivery only had recently. Citations co-citation achievements clarified cluster #0 induced pluripotent cells, #2 mesenchymal #3 microglia, #6 adult hippocampal neurogenesis persisted recent time. Conclusion: This provides comprehensive guide clinicians scholars working These results hope provide useful information references understanding challenges behind translating underlying biology into novel clinical potential AD.
Language: Английский
Citations
20
Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 102026 - 102026
Published: July 31, 2023
Since the discovery of mechanosensitive Piezo1 channel in 2010, there has been a significant amount research conducted to explore its regulatory role physiology and pathology various organ systems. Recently, growing body compelling evidence emerged linking activity health disease central nervous system. However, exact mechanisms underlying these associations remain inadequately comprehended. This review systematically summarizes current on implications for system mechanobiology, retrospects results demonstrating cell types within system, including neural stem cells, neurons, oligodendrocytes, microglia, astrocytes, brain endothelial cells. Furthermore, discusses understanding involvement disorders, such as Alzheimer's disease, multiple sclerosis, glaucoma, stroke, glioma.
Language: Английский
Citations
18
Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(2), P. 1089 - 1101
Published: Oct. 24, 2023
Abstract INTRODUCTION Whether the integration of eye‐tracking, gait, and corresponding dual‐task analysis can distinguish cognitive impairment (CI) patients from controls remains unclear. METHODS One thousand four hundred eighty‐one participants, including 724 CI 757 controls, were enrolled in this study. Eye movement combined with patterns, measured. The LightGBM machine learning models constructed. RESULTS A total 105 gait eye‐tracking features extracted. Forty‐six parameters, 32 14 features, showed significant differences between two groups ( P < 0.05). Of these, Gait_3Back‐TurnTime Dual‐task cost‐TurnTime patterns significantly correlated plasma phosphorylated tau 181 (p‐tau181) level. model based on smooth pursuit, prosaccade, anti‐saccade achieved best area under receiver operating characteristics curve (AUC) 0.987 for detection, while p‐tau181, discriminated mild an AUC 0.824. DISCUSSION Combining is feasible detection CI. Highlights This first study to report efficiency integrated parameters a large cohort. We identified 46 associated CI, 181. constructed anti‐saccade, achieving detection.
Language: Английский
Citations
18