ProNGF elicits retrograde axonal degeneration of basal forebrain neurons through p75NTR and induction of amyloid precursor protein.
Sci Signal
; 17(855): eadn2616, 2024 Sep 24.
Article
en En
| MEDLINE
| ID: mdl-39316663
ABSTRACT
Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple regions in the brain to regulate cognitive functions. Degeneration of BFCNs is seen with aging, after brain injury, and in neurodegenerative disorders. An increase in the amount of the immature proform of nerve growth factor (proNGF) in the cerebral cortex results in retrograde degeneration of BFCNs through activation of proNGF receptor p75NTR. Here, we investigated the signaling cascades initiated at the axon terminal that mediate proNGF-induced retrograde degeneration. We found that local axonal protein synthesis and retrograde transport mediated proNGF-induced degeneration initiated from the axon terminal. Analysis of the nascent axonal proteome revealed that proNGF stimulation of axonal terminals triggered the synthesis of numerous proteins within the axon, and pathway analysis showed that amyloid precursor protein (APP) was a key upstream regulator in cultured BFCNs and in mice. Our findings reveal a functional role for APP in mediating BFCN axonal degeneration and cell death induced by proNGF.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Axones
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Precursor de Proteína beta-Amiloide
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Factor de Crecimiento Nervioso
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Prosencéfalo Basal
Límite:
Animals
Idioma:
En
Revista:
Sci Signal
Asunto de la revista:
CIENCIA
/
FISIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos