Not just amyloid: physiological functions of the amyloid precursor protein family

Nature reviews. Neuroscience, Год журнала: 2017, Номер 18(5), С. 281 - 298

Опубликована: Март 31, 2017

Язык: Английский

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Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease

Neuropeptides, Год журнала: 2015, Номер 52, С. 1 - 18

Опубликована: Июль 4, 2015

Язык: Английский

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Presenilins and -Secretase: Structure, Function, and Role in Alzheimer Disease

Cold Spring Harbor Perspectives in Medicine, Год журнала: 2011, Номер 2(1), С. a006304 - a006304

Опубликована: Ноя. 8, 2011

Presenilins were first discovered as sites of missense mutations responsible for early-onset Alzheimer disease (AD). The encoded multipass membrane proteins subsequently found to be the catalytic components γ-secretases, membrane-embedded aspartyl protease complexes generating carboxyl terminus amyloid β-protein (Aβ) from protein precursor (APP). complex also cleaves a variety other type I integral proteins, most notably Notch receptor, signaling which is involved in many cell differentiation events. Although γ-secretase top target developing disease-modifying AD therapeutics, interference with should avoided. Compounds that alter Aβ production by without affecting proteolysis and have been identified are currently at various stages drug development pipeline.

Язык: Английский

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The Amyloid Cascade Hypothesis in Alzheimer’s Disease: It’s Time to Change Our Mind

Current Neuropharmacology, Год журнала: 2017, Номер 15(6)

Опубликована: Июль 31, 2017

Since its discovery in 1984, the beta amyloid peptide has treaded boards of neurosciences as star molecule Alzheimer’s disease pathogenesis. In last decade, however, this vision been challenged by evidence-based medicine showing almost complete failure clinical trials that experimented anti-amyloid therapies with great hopes. Moreover, data have accumulated which clearly indicate small plays a key role physiological processes memory formation. present review, we will discuss different aspects cascade hypothesis, highlighting pros and cons, analyse results therapeutic approaches attempted to date should change direction research future. Keywords: Alzheimer's disease, amyloid, trials, LTP, memory, therapy.

Язык: Английский

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Imbalance between firing homeostasis and synaptic plasticity drives early-phase Alzheimer’s disease

Nature Neuroscience, Год журнала: 2018, Номер 21(4), С. 463 - 473

Опубликована: Фев. 5, 2018

Язык: Английский

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Insights into the physiological function of the β‐amyloid precursor protein: beyond Alzheimer's disease

Journal of Neurochemistry, Год журнала: 2014, Номер 129(5), С. 756 - 769

Опубликована: Фев. 12, 2014

Abstract The β‐amyloid precursor protein ( APP ) has been extensively studied for its role as the of (Aβ) Alzheimer's disease. However, normal function remains largely unknown. This article reviews studies on structure, expression and post‐translational processing , well effects in vitro vivo . We conclude that published data provide strong evidence a trophic function. is likely to be involved neural stem cell development, neuronal survival, neurite outgrowth neurorepair. mechanisms by which exerts actions remain elucidated. available suggests interacts both intracellularly extracellularly regulate various signal transduction mechanisms. image (APP), vivo.

Язык: Английский

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Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

Chemical Communications, Год журнала: 2015, Номер 51(70), С. 13434 - 13450

Опубликована: Янв. 1, 2015

Our Feature Article details the physiological role of amyloid beta (Aβ), elaborates its toxic effects and outlines therapeutic molecules designed in last two years targeting different aspects Aβ for preventing AD.

Язык: Английский

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Noncoding RNAs in Alzheimer's disease

Wiley Interdisciplinary Reviews - RNA, Год журнала: 2018, Номер 9(2)

Опубликована: Янв. 12, 2018

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia among elderly worldwide. Despite intense efforts to develop drugs for preventing treating AD, no effective therapies are available as yet, posing growing burden at personal, medical, socioeconomic levels. AD characterized by production aggregation amyloid β (Aβ) peptides derived from precursor protein (APP), presence hyperphosphorylated microtubule-associated Tau (MAPT), chronic inflammation leading neuronal loss. Aβ accumulation responsible histopathological features plaques, neurofibrillary tangles (NFTs), respectively. However, full spectrum molecular factors that contribute pathogenesis not known. Noncoding (nc)RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular (circRNAs), regulate gene expression transcriptional posttranscriptional levels in various diseases, serving biomarkers potential therapeutic targets. There rising recognition ncRNAs have been implicated both onset AD. Here, we review posttranscriptionally pathways discuss interest targeting regulatory therapeutically combat pathology. WIREs RNA 2018, 9:e1463. doi: 10.1002/wrna.1463 This article categorized under: Disease Development > Disease.

Язык: Английский

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Role of Amyloid-β and Tau Proteins in Alzheimer’s Disease: Confuting the Amyloid Cascade

Journal of Alzheimer s Disease, Год журнала: 2018, Номер 64(s1), С. S611 - S631

Опубликована: Май 29, 2018

The "Amyloid Cascade Hypothesis" has dominated the Alzheimer's disease (AD) field in last 25 years. It posits that increase of amyloid-β (Aβ) is key event AD triggers tau pathology followed by neuronal death and eventually, disease. However, therapeutic approaches aimed at d ecreasing Aβ levels have so far failed, tau-based clinical trials not yet produced positive findings. This begs question whether hypothesis correct. Here we examined literature on role synaptic dysfunction, memory loss, seeding spreading AD, highlighting important parallelisms between two proteins all these phenomena. We discuss novel findings showing binding both oligomers to protein precursor (AβPP), requirement for presence this enter neurons induce abnormal function memory. Most importantly, propose a view pathogenesis which extracellular act parallel upstream AβPP. Such will call reconsideration directed against tau, paving way an increased interest toward AβPP, understanding elaborating new strategies.

Язык: Английский

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Physiology and pharmacology of amyloid precursor protein

Pharmacology & Therapeutics, Год журнала: 2022, Номер 235, С. 108122 - 108122

Опубликована: Фев. 1, 2022

Язык: Английский

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