TGR5 deficiency in excitatory neurons ameliorates Alzheimer’s pathology by regulating APP processing DOI Creative Commons
Chenli Li, Liangjie Wang,

Wenting Xie

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(26)

Published: June 28, 2024

Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer’s disease (AD). We found that deoxycholic acid (DCA) increased in brains AD mice at an early stage. The enhanced production DCA induces up-regulation bile receptor Takeda G protein-coupled (TGR5), which is also specifically neurons mouse accumulation exogenous impairs cognitive function wild-type mice, but not TGR5 knockout mice. This suggests primary mediating these effects DCA. Furthermore, excitatory neuron-specific ameliorates Aβ pathology and cognition impairments underlying mechanism linking relies downstream effectors APP production, succinctly concluded as “p-STAT3–APH1–γ-secretase” signaling pathway. Our studies identified critical role pathological development AD.

Language: Английский

Liposome-Derived Nanosystems for the Treatment of Behavioral and Neurodegenerative Diseases: The Promise of Niosomes, Transfersomes, and Ethosomes for Increased Brain Drug Bioavailability DOI Creative Commons
Patrícia C. Pires, Ana Cláudia Paiva‐Santos, Francisco Veiga

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(10), P. 1424 - 1424

Published: Oct. 8, 2023

Psychiatric and neurodegenerative disorders are amongst the most prevalent debilitating diseases, but current treatments either have low success rates, greatly due to permeability of blood–brain barrier, and/or connected severe side effects. Hence, new strategies extremely important, here is where liposome-derived nanosystems come in. Niosomes, transfersomes, ethosomes nanometric vesicular structures that allow drug encapsulation, protecting them from degradation, increasing their solubility, permeability, brain targeting, bioavailability. This review highlighted great potential these for treatment Alzheimer’s disease, Parkinson’s schizophrenia, bipolar disorder, anxiety, depression. Studies regarding encapsulation synthetic natural-derived molecules in systems, intravenous, oral, transdermal, or intranasal administration, led an increased bioavailability when compared conventional pharmaceutical forms. Moreover, developed formulations proved neuroprotective, anti-inflammatory, antioxidant effects, including neurotransmitter level restoration oxidative status improvement, improved locomotor activity enhancement recognition working memories animal models. albeit being relatively technologies, niosomes, already proven increase psychoactive drugs, leading effectiveness decreased showing promise as future therapeutics.

Language: Английский

Citations

20
The Aging Enteric Nervous System DOI Open Access
Tinh Thi Nguyen, Peter Baumann,

Oliver Tüscher

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9471 - 9471

Published: May 30, 2023

The gut and the brain communicate via nervous system, hormones, microbiota-mediated substances, immune system. These intricate interactions have led to term “gut-brain axis”. Unlike brain—which is somewhat protected—the exposed a variety of factors throughout life and, consequently, might be either more vulnerable or better adapted respond these challenges. Alterations in function are common elder population associated with many human pathologies, including neurodegenerative diseases. Different studies suggest that changes system gut, enteric (ENS), during aging may result gastrointestinal dysfunction initiate pathologies its interconnection gut. This review aims at summarizing contribution normal cellular age-associated physiological ENS. Morphological alterations degeneration ENS observed different animal models humans, albeit considerable variability. phenotypes pathophysiological mechanisms highlighted involvement neurons age-related diseases central such as Alzheimer’s Parkinson’s disease. To further elucidate mechanisms, constitutes promising source material for diagnosis therapeutic predictions, it accessible than brain.

Language: Английский

Citations

18
Etiology, pathogenesis of Alzheimer's disease and amyloid beta hypothesis DOI
Sarika M. Kamble, Kalpesh R. Patil, Aman B. Upaganlawar

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: Jan. 1, 2024

Language: Английский

Citations

7
Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer’s Disease DOI Open Access
Lynn Pulliam,

Bing Sun,

Erin McCafferty

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3830 - 3830

Published: March 29, 2024

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people LongC contained proteins Alzheimer’s disease (AD). Since time, subset prior infection continue to report neurological problems more than three months after infection. Blood markers better characterize are elusive. To further identify neuronal LongC, we maximized number nEVs isolated plasma by developing hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. and complaints, AD, HIV mild Using OLINK platform assesses 384 proteins, identified 11 significant increased in 2 decreased (BST1, GGT1). Fourteen were AD forty impairment elevated one (IVD). One common protein (BST1) was HIV. Six (MIF, ENO1, MESD, NUDT5, TNFSF14 FYB1) expressed both no AD. This study begins differences similarities response versus

Language: Английский

Citations

6
TGR5 deficiency in excitatory neurons ameliorates Alzheimer’s pathology by regulating APP processing DOI Creative Commons
Chenli Li, Liangjie Wang,

Wenting Xie

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(26)

Published: June 28, 2024

Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer’s disease (AD). We found that deoxycholic acid (DCA) increased in brains AD mice at an early stage. The enhanced production DCA induces up-regulation bile receptor Takeda G protein-coupled (TGR5), which is also specifically neurons mouse accumulation exogenous impairs cognitive function wild-type mice, but not TGR5 knockout mice. This suggests primary mediating these effects DCA. Furthermore, excitatory neuron-specific ameliorates Aβ pathology and cognition impairments underlying mechanism linking relies downstream effectors APP production, succinctly concluded as “p-STAT3–APH1–γ-secretase” signaling pathway. Our studies identified critical role pathological development AD.

Language: Английский

Citations

6