The amyloid precursor protein and postnatal neurogenesis/neuroregeneration.
The amyloid precursor protein (APP) is the source of amyloid-beta (Abeta) peptide, produced via its sequential cleavage beta- and gamma-secretases. Various biophysical forms of Abeta (and the mutations of APP which results in their elevated levels) have been implicated in the etiology and early onset of Alzheimer's disease. APP's evolutionary conservation and the existence of APP-like isoforms (APLP1 and APLP2) which lack the Abeta sequence, however, suggest that these might have important physiological functions that are unrelated to Abeta production. Soluble N-terminal fragments of APP have been known to be neuroprotective, and the interaction of its cytoplasmic C-terminus with a myriad of proteins associates it with diverse processes such as axonal transport and transcriptional regulation. The notion for an essential postnatal function of APP has been demonstrated genetically, as mice deficient in both APP and APLP2 or all three APP isoforms exhibit early postnatal lethality and neuroanatomical abnormalities. Recent findings have also brought to light two possible functions of the APP family in the brain-regulation of neural progenitor cell proliferation and axonal outgrowth after injury. Interestingly, these two apparently related neurogenic/neuroregenerative functions of APP involve two separate domains of the molecule.
Chen
Yanan
Y
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Tang
Bor Luen
BL
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry
D016564:Amyloid beta-Protein Precursor; D020033:Protein Isoforms