The Alzheimer’s Disease Amyloid Precursor Protein and its Neuritogenic Actions

Abstract

: The Amyloid Precursor Protein (APP) is principally known and studied for its involve- ment in Alzheimer’s disease as the source of the amyloid β peptide; however, its physiological ac- tions within the nervous system are also important as it is involved in a range of neuronal activi- ties, including neurogenesis, synaptic plasticity, neurite outgrowth, and neuroprotection. Of the dif- ferent neuronal functions that APP can affect, some may be relevant to APP’s role in Alzheimer’s disease, while others can be primarily related to its physiological roles. This review will focus on APP’s neuritogenic actions and surmise the key molecular mechanisms, as well as the structural and signaling requirements, which form the basis for APP’s neuritogenic effects. Deciphering the normal function(s) of APP is valuable to properly understanding its role in health as well as Alzheimer’s disease.

Screening and identification of biomarkers associated with the immune infiltration of intracerebral hemorrhage

“…The accumulation of Aβ leads to the disorder of cellular calcium signaling and malfunctioning of mitochondria, which in turn leads to the loss of synapses and the death of neurons, as well as a series of neuroinflammation. 34 There was little research on the role of APP in ICH, platelet growth factor of the CXC chemotherapy family. PPBP is released from activated platelets and is proved to be potential novel biomarker for multiple tumors.…”

“…The accumulation of Aβ leads to the disorder of cellular calcium signaling and malfunctioning of mitochondria, which in turn leads to the loss of synapses and the death of neurons, as well as a series of neuroinflammation. 34 There was little research on the role of APP in ICH, especially the immune mechanism involved in the progression of cerebral hemorrhage. Therefore, APP as a potential target deserves further study.…”

“…Partial mutation of APP can lead to increased Aβ production, or Aβ more prone to aggregation. The accumulation of Aβ leads to the disorder of cellular calcium signaling and malfunctioning of mitochondria, which in turn leads to the loss of synapses and the death of neurons, as well as a series of neuroinflammation 34 …”

Recent Advances in Our Molecular and Mechanistic Understanding of Misfolded Cellular Proteins in Alzheimer’s Disease (AD) and Prion Disease (PrD)

“…The 695–751 amino acid beta-amyloid precursor protein (βAPP; encoded at human chromosome 21q21.3; ; last accessed 18 January 2022), a Type 1 integral trans-membrane protein, is endoproteolytically processed to generate either the neurotrophic secreted ectodomain constituting APP alpha (sAPPα) or a series of ragged, neurotoxic, amyoidogenic amyloid beta (Aβ) peptides [ 18 , 19 ]. The 40–42 amino acid amyloid-beta (Aβ40, Aβ42) peptides and other oligomeric Aβ species are derived from the sequential tandem endoproteolytic cleavage of βAPP by the amyloidogenic beta- and gamma-secretases [ 18 , 19 , 20 , 21 ]. While the neurobiology and neurophysiology of βAPP holoprotein is incompletely understood, βAPP’s most recent functional assignments include essential roles in cellular adhesion, neural growth and repair, neurogenesis, synaptic plasticity, neurite outgrowth and/or neuroprotection, and many of these neurotrophic functions are moderated by the α-secretase-mediated βAPP ectodomain cleavage into sAPPα [ 17 , 18 , 20 , 21 ].…”

“…The 40–42 amino acid amyloid-beta (Aβ40, Aβ42) peptides and other oligomeric Aβ species are derived from the sequential tandem endoproteolytic cleavage of βAPP by the amyloidogenic beta- and gamma-secretases [ 18 , 19 , 20 , 21 ]. While the neurobiology and neurophysiology of βAPP holoprotein is incompletely understood, βAPP’s most recent functional assignments include essential roles in cellular adhesion, neural growth and repair, neurogenesis, synaptic plasticity, neurite outgrowth and/or neuroprotection, and many of these neurotrophic functions are moderated by the α-secretase-mediated βAPP ectodomain cleavage into sAPPα [ 17 , 18 , 20 , 21 ].…”