Alpha Secretase - Histology

What is Alpha Secretase?

Alpha secretase is a type of protease enzyme that plays a critical role in the proteolytic processing of certain membrane proteins. It is notably involved in the processing of the amyloid precursor protein (APP), a protein associated with the pathogenesis of Alzheimer's disease. By cleaving APP within its amyloid-beta domain, alpha secretase prevents the formation of amyloid-beta peptides, which are implicated in Alzheimer's disease.

Where is Alpha Secretase Found?

Alpha secretase activity is widely distributed in the central nervous system and peripheral tissues. It is particularly abundant in neurons, where it plays a role in synaptic function and neuronal communication. The enzyme is also present in various other tissues, including the heart, liver, and muscles.

What are the Functions of Alpha Secretase?

The primary function of alpha secretase is to cleave membrane proteins, thereby regulating their function and turnover. In the context of APP, alpha secretase cleavage prevents the formation of toxic amyloid-beta peptides. This activity is part of the non-amyloidogenic pathway of APP processing. Additionally, alpha secretase is involved in the shedding of cell surface receptors and the release of signaling molecules, which are crucial for cell communication and signaling pathways.

How is Alpha Secretase Regulated?

The activity of alpha secretase is regulated at multiple levels, including gene expression, post-translational modifications, and subcellular localization. Various factors such as growth factors, cytokines, and neurotransmitters can modulate its activity. Furthermore, the enzyme's activity can be influenced by lipid rafts and membrane microdomains, which provide a platform for its function.

What is the Clinical Significance of Alpha Secretase?

Given its role in preventing amyloid-beta formation, alpha secretase is a potential therapeutic target for Alzheimer's disease. Enhancing alpha secretase activity could reduce amyloid-beta levels and mitigate disease progression. Additionally, alpha secretase is involved in the shedding of several cell adhesion molecules and growth factor receptors, making it relevant in other pathologies such as cancer and cardiovascular diseases.

What are the Challenges and Future Directions?

One of the challenges in targeting alpha secretase for therapeutic purposes is achieving specificity without affecting its other physiological functions. Future research aims to develop selective modulators or activators that can enhance its beneficial effects while minimizing potential side effects. Understanding the structural biology of alpha secretase and its interaction with substrates will be crucial in developing these targeted therapies.

Relevant Publications

Plasma ADAM10 Levels and their Association with Alzheimer\'s Disease Diagnosis in Older Adults with Fewer Years of Formal Education.

Issue Release: 2024

Alpha-lipoic acid alleviates cognitive deficits in transgenic APP23/PS45 mice through a mitophagy-mediated increase in ADAM10 α-secretase cleavage of APP.

Issue Release: 2024

Correction to \"Constitutive alpha-secretase cleavage of the beta-amyloid precursor protein in the furin-deficient LoVo cell line: involvement of the pro-hormone convertase 7 and the disintegrin and metalloprotease ADAM10\".

Issue Release: 2024

Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer\'s Disease with Survival up to 2 Years.

Issue Release: 2024

m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways.

Issue Release: 2024

Alpha-secretase inhibition impairs Group I metabotropic glutamate receptor-mediated protein synthesis, long-term potentiation and long-term depression.

Issue Release: 2024

The roles of RACK1 in the pathogenesis of Alzheimer\'s disease.

Issue Release: 2024

Utility of human induced pluripotent stem cell-derived small intestinal epithelial cells for pharmacokinetic, toxicological, and immunological studies.

Issue Release: 2023

Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel.

Issue Release: 2023

Activation of TNF Receptor 2 Improves Synaptic Plasticity and Enhances Amyloid-β Clearance in an Alzheimer\'s Disease Mouse Model with Humanized TNF Receptor 2.

Issue Release: 2023

Design, Synthesis, and Biological Evaluation of Piperazine and -Benzylpiperidine Hybrids of 5-Phenyl-1,3,4-oxadiazol-2-thiol as Potential Multitargeted Ligands for Alzheimer\'s Disease Therapy.

Issue Release: 2023

Aerial part of Houttuynia cordata reverses memory impairment by regulating amyloid beta accumulation and neuroinflammation in Alzheimer\'s disease model.

Issue Release: 2023

Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: an integrated computational analysis.

Issue Release: 2023

Alpha-secretase dependent nuclear localization of the amyloid-β precursor protein-binding protein Fe65 promotes DNA repair.

Issue Release: 2023

Notch3 deletion regulates HIV-1 gene expression and systemic inflammation to ameliorate chronic kidney disease.

Issue Release: 2023

The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration.

Issue Release: 2023

The Connection between Chronic Liver Damage and Sporadic Alzheimer\'s Disease: Evidence and Insights from a Rat Model.

Issue Release: 2023

Human platelets release amyloid peptides β and β in response to haemostatic, immune, and hypoxic stimuli.

Issue Release: 2023

Autophagy in age-related macular degeneration.

Issue Release: 2022

Expression of Amyloid Precursor Protein, Caveolin-1, Alpha-, Beta-, and Gamma-Secretases in Penumbra Cells after Photothrombotic Stroke and Evaluation of Neuroprotective Effect of Secretase and Caveolin-1 Inhibitors.

Issue Release: 2022

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