Bace1 modulates myelination in the central and peripheral nervous system

Xiangyou Hu, Caitlin Hicks, Wanxia He, Philip Chun Wong, Wendy B. MacKlin, Bruce D. Trapp, Riqiang Yan

Research output: Contribution to journalArticle

Abstract

Bace1 is an endopeptidase that cleaves the amyloid precursor protein at the β-secretase site. Apart from this cleavage, the functional importance of Bace1 in other physiological events is unknown. We show here that Bace1 regulates the process of myelination and myelin sheath thickness in the central and peripheral nerves. In Bace1-null mice, the process of myelination was delayed and myelin thickness was markedly reduced, indicating that genetic deletion of Bace1 causes hypomyelination. Bace1-null mice also showed altered neurological behaviors such as elevated pain sensitivity and reduced grip strength. Further mechanistic studies showed an altered neuregulin-Akt signaling pathway in Bace1-null mice. Full-length neuregulin-1 was increased and its cleavage product was decreased in the CNS of Bace1-null mice. Furthermore, phosphorylated Akt was also reduced. Based upon these and previous studies, we postulate that neuronally enriched Bace1 cleaves neuregulin-1 and that processed neuregulin-1 regulates myelination by means of phosphorylation of Akt in myelin-forming cells.

Original languageEnglish (US)
Pages (from-to)1520-1525
Number of pages6
JournalNature Neuroscience
Volume9
Issue number12
DOIs
StatePublished - Dec 2006

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Peripheral Nervous System
Neuregulin-1
Central Nervous System
Myelin Sheath
Neuregulins
Endopeptidases
Amyloid Precursor Protein Secretases
Hand Strength
Peripheral Nerves
Phosphorylation
Pain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bace1 modulates myelination in the central and peripheral nervous system. / Hu, Xiangyou; Hicks, Caitlin; He, Wanxia; Wong, Philip Chun; MacKlin, Wendy B.; Trapp, Bruce D.; Yan, Riqiang.

In: Nature Neuroscience, Vol. 9, No. 12, 12.2006, p. 1520-1525.

Research output: Contribution to journalArticle

Hu, Xiangyou ; Hicks, Caitlin ; He, Wanxia ; Wong, Philip Chun ; MacKlin, Wendy B. ; Trapp, Bruce D. ; Yan, Riqiang. / Bace1 modulates myelination in the central and peripheral nervous system. In: Nature Neuroscience. 2006 ; Vol. 9, No. 12. pp. 1520-1525.
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