Table 2.
Functions of APP fragments in the mammalian CNS.
| APP fragment | Functions and effects | Reference |
|---|---|---|
| sAPPα | LTP and NMDAR currents in DG of anesthetized rats; | [220-222] |
| Rescues spine density of APP organotypic hippocampal cultures; rescues LTP and spatial learning in aged APP mice; | [223, 224] | |
| Tg OE in APP/PS1 mice inhibits the amyloidogenic pathway, reduces plaque deposition and reduces GSK3β-dependent tau phosphorylation; | [225] | |
| Protects against TBI; neuronal death during transient ischemia; and hypoxia in acute hippocampal slices; Stimulates aduit neurogenesis at the subventricular zone; | [226, 227] | |
| sAPPβ | Stable metabolite in vivo, not associated with increased cell death, induces transcription of transthyretin and klotho; |
[228, 229] |
| Aβ* | Generated by meprin cleavage, High aggregation propensity: potential seed for Aβ deposition; | [115, 117] |
| p3 | Physiological or trophic function unknown; no pathological effects reported; | [230] |
| Aη-α | Neuronal activity and LTP in wild-type hippocampal slices, Upregulated upon β-secretae inhibition; | [231] |
| Aη-β | None of the pathological properties reported; | [232] |
| APPsη | Physiological function unknown; | [233] |
| APPsσ | Tg AD model mice that also lack σ-secretase show reduced Aβ load and ameliorated functional deficits; | [234] |
| sAPPβ* | Generated by meprin cleavage, physiological function unknown; | [235] |
| CTFα | Physiological function unknown; | [236] |
| CTFβ | Injection of CTFβ impairs working memory and induces neurodegeneration and gliosis; Tg CTFβ OE induces neurodegeneration, reduces LTP and impairs cognition, impairs lysosomal autophagic function; | [237] |
| CTFη | Associated with plaques. upregulated upon β-secretase inhibition; | [118] |
| C31 | C31 complexes with APP to recruit the interacting partners that initiate the signals related to cellular toxicity; | [238, 239] |
| Jcasp | Intracelular delivery to acute hippocampal slices reduces basal synaptic transmission, increases PPF and synaptic frequency facilitation in wild-type, but not in APP, mice, and reduces the rate; | [239, 240] |
Aβ, amyloid; Aβ*2-x, the peptide beginning with amino acid 2 of Aβ; AD, Alzheimer's disease. AICD, APP intracellular domain; sAPPβ*, one amino acid longer than sAPPβ generated by β-secretase cleavage; CTF, C-terminal fragment; DG, dentate gyrus; APP, amyloid precursor protein; CTF nAChR, nicotinic acetylcholine receptor; GSK3, glycogen synthase kinase 3; NMDAR, NMDA receptor; OE, overexpression; PTP, posttetanic potentiation; PPF, paired-pulse facilitation; LTP, long-term potentiation; Tg, transgenic; TBI, traumatic brain injury