Bace1 modulates myelination in the central and peripheral nervous system

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Beta-site amyloid precursor protein cleaving enzyme 1 (Bace1) is known for cleaving amyloid precursor protein.
• The broader physiological roles of Bace1 beyond amyloid processing remain largely unexplored.

Purpose of the Study:

• To investigate the function of Bace1 in myelination and associated neurological processes.
• To elucidate the molecular mechanisms by which Bace1 influences myelination.

Main Methods:

• Utilized Bace1-null mice to assess myelination and neurological behaviors.
• Analyzed the neuregulin-1/Akt signaling pathway in the central nervous system (CNS) of Bace1-null mice.

Main Results:

• Bace1-null mice displayed delayed myelination and reduced myelin thickness (hypomyelination).
• These mice exhibited altered neurological functions, including increased pain sensitivity and decreased grip strength.
• Bace1 deficiency led to increased full-length neuregulin-1 and decreased its cleavage product in the CNS, alongside reduced phosphorylated Akt levels.

Conclusions:

• Bace1 plays a critical role in regulating myelination and myelin sheath thickness in both central and peripheral nerves.
• Neuronally expressed Bace1 likely cleaves neuregulin-1, and the processed neuregulin-1 subsequently modulates myelination via Akt phosphorylation in myelin-forming cells.