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

Hayder M Al-Kuraishy; Majid S Jabir; Ali I Al-Gareeb; Ali K Albuhadily; Salim Albukhaty; Ghassan M Sulaiman; Gaber El-Saber Batiha

doi:10.1016/j.arr.2023.102119

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

Ageing Res Rev. 2023 Dec:92:102119. doi: 10.1016/j.arr.2023.102119. Epub 2023 Nov 4.

Authors

Hayder M Al-Kuraishy¹, Majid S Jabir², Ali I Al-Gareeb¹, Ali K Albuhadily¹, Salim Albukhaty³, Ghassan M Sulaiman⁴, Gaber El-Saber Batiha⁵

Affiliations

¹ Department of Clinical pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
² Department of Applied science, University of Technology, Iraq. Electronic address: 100131@uotechnology.edu.iq.
³ Department of Chemistry, College of Science, University of Misan, Maysan 62001, Iraq.
⁴ Department of Applied science, University of Technology, Iraq.
⁵ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira 22511, Egypt.

PMID: 37931848
DOI: 10.1016/j.arr.2023.102119

Abstract

In Alzheimer disease (AD), amyloid precursor protein (APP) and production of amyloid beta (Aβ) which is generated by amyloidogenic pathway is implicated in neurotoxicity and neuronal cell deaths. However, physiological Aβ level is essential to improves neuronal survival, attenuates neuronal apoptosis and has neuroprotective effect. In addition, physiological APP level has neurotrophic effect on the central nervous system (CNS). APP has a critical role in the brain growth and development via activation of long-term potentiation (LTP) and acceleration of neurite outgrowth. Moreover, APP is cleaved by α secretase to form a neuroprotective soluble APP alpha (sAPPα) in non-amyloidogenic pathway. Consequently, this mini-review purposes to highlight the possible beneficial role of APP and Aβ. In addition, this mini-review discussed the modulation of APP processing and Aβ production.

Keywords: Alzheimer disease; Amyloid beta; Amyloid precursor protein; Amyloidogenic pathway; Non-amyloidogenic pathway.

Publication types

Review

MeSH terms

Alzheimer Disease* / metabolism
Amyloid Precursor Protein Secretases / metabolism
Amyloid beta-Peptides / metabolism
Amyloid beta-Protein Precursor* / metabolism
Brain / metabolism
Humans

Substances

Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Amyloid Precursor Protein Secretases