Results 11 to 20 of about 26,551 (120)

Hair Cell Generation in Cochlear Culture Models Mediated by Novel γ-Secretase Inhibitors [PDF]

Frontiers in Cell and Developmental Biology, 2021
Sensorineural hearing loss is prevalent within society affecting the quality of life of 460 million worldwide. In the majority of cases, this is due to insult or degeneration of mechanosensory hair cells in the cochlea. In adult mammals, hair cell loss is irreversible as sensory cells are not replaced spontaneously.
Silvia T. Erni, Silvia T. Erni, Silvia T. Erni, Silvia T. Erni, John C. Gill, Carlotta Palaferri, Carlotta Palaferri, Carlotta Palaferri, Gabriella Fernandes, Gabriella Fernandes, Gabriella Fernandes, Michelle Buri, Michelle Buri, Michelle Buri, Katherine Lazarides, Denis Grandgirard, Denis Grandgirard, Albert S. B. Edge, Albert S. B. Edge, Albert S. B. Edge, Stephen L. Leib, Stephen L. Leib, Marta Roccio, Marta Roccio, Marta Roccio, Marta Roccio   +25 more
openaire   +4 more sources

The γ-secretase complex: from structure to function [PDF]

Frontiers in Cellular Neuroscience, 2014
One of the most critical pathological features of Alzheimer's disease (AD) is the accumulation of β-amyloid (Aβ) peptides that form extracellular senile plaques in the brain. Aβ is derived from β-amyloid precursor protein (APP) through sequential cleavage by β- and γ-secretases.
Xian eZhang, Yanfang eLi, Huaxi eXu, Huaxi eXu, Yun-Wu eZhang   +4 more
openaire   +3 more sources

Complex regulation of γ-secretase: from obligatory to modulatory subunits [PDF]

Frontiers in Aging Neuroscience, 2015
γ-Secretase is a four subunit, 19-pass transmembrane enzyme that cleaves amyloid precursor protein (APP), catalyzing the formation of amyloid beta (Aβ) peptides that form amyloid plaques, which contribute to Alzheimer's disease (AD) pathogenesis. γ-Secretase also cleaves Notch, among many other type I transmembrane substrates.
Gertsik, Natalya, Chiu, Danica, Li, Yue-Ming   +2 more
openaire   +3 more sources

β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease [PDF]

Frontiers in Aging Neuroscience, 2014
Alzheimer's disease (AD) and vascular dementia are responsible for up to 90% of dementia cases. According to the World Health Organization (WHO), a staggering number of 35.6 million people are currently diagnosed with dementia. Blocking disease progression or preventing AD altogether is desirable for both social and economic reasons and recently focus ...
Menting, K.W., Claassen, J.A.H.R.
openaire   +3 more sources

APP intracellular domain derived from amyloidogenic β- and γ-secretase cleavage regulates neprilysin expression [PDF]

Frontiers in Aging Neuroscience, 2015
Alzheimer's disease (AD) is characterized by an accumulation of Amyloid-β (Aβ), released by sequential proteolytic processing of the amyloid precursor protein (APP) by β - and γ-secretase. Aβ peptides can aggregate, leading to toxic Aβ oligomers and amyloid plaque formation.
Grimm, Marcus O. W., Mett, Janine, Stahlmann, Christoph P., Grösgen, Sven, Haupenthal, Viola J., Blümel, Tamara, Hundsdörfer, Benjamin, Zimmer, Valerie C., Mylonas, Nadine T., Tanila, Heikki, Müller, Ulrike, Grimm, Heike S., Hartmann, Tobias   +12 more
openaire   +3 more sources

Molecular mechanism of the intramembrane cleavage of the β-carboxyl terminal fragment of amyloid precursor protein by γ-secretase [PDF]

Frontiers in Physiology, 2014
Amyloid β-protein (Aβ) plays a central role in the pathogenesis of Alzheimer's disease, the most common age-associated neurodegenerative disorder. Aβ is generated through intramembrane proteolysis of the β-carboxyl terminal fragment (βCTF) of β-amyloid precursor protein (APP) by γ-secretase.
openaire   +3 more sources

Determination of the Proteolytic Cleavage Sites of the Amyloid Precursor-Like Protein 2 by the Proteases ADAM10, BACE1 and γ-Secretase

PLoS ONE, 2011
Regulated intramembrane proteolysis of the amyloid precursor protein (APP) by the protease activities α-, β- and γ-secretase controls the generation of the neurotoxic amyloid β peptide. APLP2, the amyloid precursor-like protein 2, is a homolog of APP, which shows functional overlap with APP, but lacks an amyloid β domain.
Hogl, Sebastian, Kuhn, Peer-Hendrik, Colombo, Alessio, Lichtenthaler, Stefan F.   +3 more
openaire   +6 more sources

GPCRs in CAR‐T Cell Immunotherapy: Expanding the Target Landscape and Enhancing Therapeutic Efficacy

Advanced Science, EarlyView.
Chimeric antigen receptor T cell therapy faces dual challenges of target scarcity and an immunosuppressive microenvironment in solid tumors. This review highlights how G protein‐coupled receptors can serve as both novel targets to expand the therapeutic scope and functional modules to enhance CAR‐T cell efficacy.
Zhuoqun Liu, Yuchen Xiao, Yamin Zhao, Lihe Dai, David J.H. Shih, Shikang Liang, Honglei Tian, Liu Liu, Feng Tian, Bing Liu, Lei Chang, Chao Zhang   +11 more
wiley   +1 more source

Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid‐β Production and Cognitive Dysfunctions in Alzheimer's Disease

Advanced Science, EarlyView.
This study explores the opposing effects of the mGluR2 and mGluR3 receptors on amyloid precursor protein processing. mGluR2 promotes amyloidogenic cleavage, while mGluR3 favors non‐amyloidogenic pathways. Using a brain‐penetrant nanobody as a mGluR2 positive allosteric modulator, the study uncovers how its chronic activation aggravates amyloid‐β burden
Pierre‐André Lafon, Mireille Elodie Tsitokana, Ugo Guy Alenda, Yen‐Ling Lian, Clémentine Eva Philibert, Mathieu Oosterlaken, Marta Cimadevila, Gaëlle Dudon, Jessica Monnic, Salomé Roux, Julie Bessié, Séverine Diem, Franck Vandermoere, Laurent Prézeau, Patrick Chames, Julie Kniazeff, Sylvie Claeysen, Anaïs Menny, Jean‐Philippe Pin, Véronique Perrier, Jianfeng Liu, Philippe Rondard   +21 more
wiley   +1 more source

BCMA‐Engineered Dendritic Cell‐Derived Exosomes as Bi‐Functional Therapeutics Orchestrating Cytokine Sequestration and Immune Activation for Multiple Myeloma

Advanced Science, EarlyView.
A dual‐function cell‐free therapeutic based on DC2.4 cell‐derived exosomes engineered to display BCMA. (Left) Soluble Ligand Sequestration (Decoy Function): DB Exo act as molecular decoys that predominantly sequester soluble APRIL with partial BAFF attenuation, effectively disrupting the NF‐κB survival signaling axis and suppressing myeloma cell ...
Yuqing Zeng, Chao He, Zhibin He, Hongbo Chen, Fang Cheng, Yongjiang Zheng   +5 more
wiley   +1 more source