The Roles of the Amyloid Beta Monomers in Physiological and Pathological Conditions DOI Creative Commons
Thomas Gabriel Schreiner,

Oliver Daniel Schreiner,

Maricel Adam

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1411 - 1411

Published: May 10, 2023

Amyloid beta peptide is an important biomarker in Alzheimer’s disease, with the amyloidogenic hypothesis as one of central hypotheses trying to explain this type dementia. Despite numerous studies, etiology disease remains incompletely known, pathological accumulation amyloid aggregates cannot fully complex clinical picture disease. Or, for development effective therapies, it mandatory understand roles at brain level, from its initial monomeric stage prior aggregation form senile plaques. In sense, review aims bring new, clinically relevant data on a subject intensely debated literature last years. first part, cascade reviewed and possible subtypes are differentiated. second played by monomers physiological (neurodegenerative) conditions illustrated based most recent studies published topic. Finally, considering importance pathophysiology new research directions diagnostic therapeutic impacts suggested.

Language: Английский

The β-Secretase BACE1 in Alzheimer’s Disease DOI Creative Commons
Harald Hampel, Robert Vassar, Bart De Strooper

et al.

Biological Psychiatry, Journal Year: 2020, Volume and Issue: 89(8), P. 745 - 756

Published: Feb. 13, 2020

BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) was initially cloned and characterized in 1999. It is required for the generation of all monomeric forms amyloid-β (Aβ), including Aβ

Language: Английский

Citations

498
Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer’s disease DOI
Pritam Thapa, Sunil P. Upadhyay,

William Z. Suo

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 108, P. 104681 - 104681

Published: Jan. 29, 2021

Language: Английский

Citations

106
The case for low-level BACE1 inhibition for the prevention of Alzheimer disease DOI
Eric McDade, Iryna Voytyuk,

Paul Aisen

et al.

Nature Reviews Neurology, Journal Year: 2021, Volume and Issue: 17(11), P. 703 - 714

Published: Sept. 21, 2021

Language: Английский

Citations

105
Alzheimer's and Parkinson's disease therapies in the clinic DOI

Puja Chopade,

Neha Chopade,

Zongmin Zhao

et al.

Bioengineering & Translational Medicine, Journal Year: 2022, Volume and Issue: 8(1)

Published: Aug. 3, 2022

Abstract Alzheimer's disease (AD) and Parkinson's (PD) are the most prevalent neurodegenerative diseases, affecting millions costing billions each year in United States alone. Despite tremendous progress developing therapeutics that manage symptoms of these two scientific community has yet to develop a treatment effectively slows down, inhibits, or cures neurodegeneration. To gain better understanding current therapeutic frontier for AD PD, we provide review on past present strategies major disorders clinical trial process. We briefly recap currently US Food Drug Administration‐approved therapies, then explore trends trials across variables therapy mechanism intervention, administration route, use delivery vehicle, outcome measures, phases over time “Drug” “Biologic” therapeutics. success rate analyze intersections approaches revealing shift away from therapies targeting neurotransmitter systems symptomatic relief, towards anti‐aggregation, anti‐inflammatory, anti‐oxidant, regeneration aim inhibit root causes progression. also highlight evolving distribution types investigated, slowly increasing still severe under‐utilization vehicles PD discuss novel preclinical treating PD. Overall, this aims succinct overview landscape understand field's strategy evolution approach present, inform how treat future.

Language: Английский

Citations

102
Safety concerns associated with BACE1 inhibitors - past, present and future DOI

Aniketh Naidu,

Bret Silverglate,

Mary Silverglate

et al.

Expert Opinion on Drug Safety, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) inhibitors have shown promise in treating Alzheimer's disease (AD) by reducing amyloid-beta (Aβ) production. However, clinical trials of like atabecestat, verubecestat, and lanabecestat faced challenges, including limited efficacy significant adverse effects. This narrative review discusses randomized-controlled inhibitors. Literature searches were conducted using PubMed Web Science for studies from 2010 to 2024. Association with BACE1's widespread expression beyond the brain shows effects such as anxiety, depressive symptoms, hepatotoxicity. The trial results underscore need CNS-specific reduce Future research should focus on optimizing drug design identifying additional therapeutic avenues, prostate cancer insulin resistance.

Language: Английский

Citations

2
Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery DOI Creative Commons
William M. Pardridge

Pharmaceuticals, Journal Year: 2020, Volume and Issue: 13(11), P. 394 - 394

Published: Nov. 16, 2020

Despite the enormity of societal and health burdens caused by Alzheimer’s disease (AD), there have been no FDA approvals for new therapeutics AD since 2003. This profound lack progress in treatment is due to dual problems, both related blood–brain barrier (BBB). First, 98% small molecule drugs do not cross BBB, ~100% biologic so BBB drug delivery technology needed development. Second, pharmaceutical industry has developed technology, which would enable invent that actually penetrate into brain parenchyma from blood. In 2020, less than 1% all development projects use a technology. The pathogenesis involves chronic neuro-inflammation, progressive deposition insoluble amyloid-beta or tau aggregates, neural degeneration. New attack these multiple sites AD, coupled with can lead effective treatments this serious disorder.

Language: Английский

Citations

139
Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer’s disease and type 2 diabetes DOI Creative Commons
Carmen Hierro‐Bujalance, Carmen Infante‐Garcia, Ángel del Marco

et al.

Alzheimer s Research & Therapy, Journal Year: 2020, Volume and Issue: 12(1)

Published: April 7, 2020

Abstract Background Both Alzheimer’s disease (AD) and type 2 diabetes (T2D) share common pathological features including inflammation, insulin signaling alterations, or vascular damage. AD has no successful treatment, the close relationship between both diseases supports study of antidiabetic drugs to limit slow down brain pathology in AD. Empagliflozin (EMP) is a sodium-glucose co-transporter inhibitor, newest class agents. EMP controls hyperglycemia reduces cardiovascular comorbidities deaths associated T2D. Therefore, we have analyzed role at central level complex mouse model AD-T2D. Methods We treated AD-T2D mice (APP/PS1xdb/db mice) with 10 mg/kg for 22 weeks. Glucose, insulin, body weight were monthly assessed. learning memory Morris water maze new object discrimination test. Postmortem assessment was conducted measure atrophy, senile plaques, amyloid-β levels. Tau phosphorylation, hemorrhage burden, microglia also measured after treatment. Results treatment helped maintain levels diabetic mice. At level, limited cortical thinning reduced neuronal loss Hemorrhage burdens EMP-treated Senile plaque burden lower, these effects accompanied by an amelioration cognitive deficits APP/PS1xdb/db Conclusions Altogether, our data support feasible reduce complications T2D, classical disease, supporting further level.

Language: Английский

Citations

135
Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease DOI Open Access
Sareer Ahmad, Myeung Hoon Jo, Muhammad Ikram

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(17), P. 9583 - 9583

Published: Sept. 3, 2021

The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ1-42)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For development an AD mouse model, (Aβ1-42, 5 μL/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice's brain by using stereotaxic frame. After that, mice treated with Luteolin for two weeks at dose 80 mg/kg/day. To monitor biochemical changes, we conducted western blotting immunofluorescence analysis. According our findings, infusion activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic (GFAP), ionized calcium adaptor molecule 1 (Iba-1) cortex hippocampus experimental mice; these changes significantly inhibited Aβ1-42 + Luteolin-treated Likewise, also checked expression inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB (Ser536), tissue necrosis factor (TNF-α), Interleukin1-β (IL-1β), Aβ1-42-injected brain, which attenuated brains. Further, investigated pro- anti-apoptotic cell death markers Bax, Bcl-2, Caspase-3, Cox-2, reduced Lut-treated brains compared Aβ-injected group. results indicated that administration Aβ1-42, levels β-site amyloid precursor cleaving enzyme (BACE-1) (Aβ1-42) enhanced, while they We PSD-95 SNAP-25, enhanced underlying factors responsible AD, used specific JNK inhibitor, suggested Aβ-associated neuroinflammation neurodegeneration via inhibition JNK. Collectively, indicate could serve novel therapeutic agent AD-like pathological

Language: Английский

Citations

70
Targeted BACE-1 inhibition in microglia enhances amyloid clearance and improved cognitive performance DOI Creative Commons
Neeraj Singh, Brati Das, John Zhou

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(29)

Published: July 20, 2022

Abnormal accumulation of β-amyloid (Aβ) peptides is a culprit in Alzheimer's disease (AD); blocking Aβ generation therefore being explored as logical approach for AD treatment. Here, we demonstrate that targeted inhibition β-site amyloid precursor protein (APP) cleaving enzyme-1 (BACE-1) microglia has unique advantages. When

Language: Английский

Citations

56
Beneficial Effects of Spirulina Consumption on Brain Health DOI Open Access
Teresa Trotta, Chiara Porro, Antonia Cianciulli

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(3), P. 676 - 676

Published: Feb. 5, 2022

Spirulina is a microscopic, filamentous cyanobacterium that grows in alkaline water bodies. It extensively utilized as nutraceutical food supplement all over the world due to its high levels of functional compounds, such phycocyanins, phenols and polysaccharides, with anti-inflammatory, antioxidant, immunomodulating properties both vivo vitro. Several scientific publications have suggested positive effects various pathologies cardiovascular diseases, hypercholesterolemia, hyperglycemia, obesity, hypertension, tumors inflammatory diseases. Lately, different studies demonstrated neuroprotective role on development neural system, senility number pathological conditions, including neurological neurodegenerative This review focuses brain, highlighting how it exerts beneficial anti-inflammatory antioxidant effects, acting glial cell activation, prevention and/or progression particular Parkinson’s disease, Alzheimer’s disease Multiple Sclerosis; these properties, could be considered potential natural drug.

Language: Английский

Citations

54