Alpha-2-macroglobulin homologues mediating nerve degeneration and regeneration

P. G. Lee, Y. O. Hu, D. J. Liebl, P. H. Koo

Research output: Contribution to journalArticlepeer-review


A number of immune/inflammatory components have been implicated in the pathogenicity of neurodegenerative diseases of the central nervous system, such as Alzheimer's disease. Alpha-2-macroglobulin (a2M) occurs as an acute-phase protein in the rat and in the human brain, and it has been implicated in Alzheimer's disease. It can covalently react with, and be "activated" by, a monoamine-neurotransmitter. The activated form, but not the unmodified form, of ttjM blocks: (1) the survival and neunte outgrowth of the central and sensory neurons, (2) the choline acetyltransferase activity of the basal forebrain neurons, (3) the development of hippocampal long-term potentiation, as well as (4) the dopaminergic system of the caudate putamen nuclei. However, similarly activated a,M can stimulate the neurite outgrowth of embryonic central neurons and the regeneration of lesioned sciatic nerve in adult rats instead. Their mechanism of inhibition and stimulation were studied. Our data showed that activated a2M and a\M dose-dependently affect neuronal functions by respectively blocking and stimulating autophosphorylation of neurotrophin receptors (trkA and IrkB), activation of intracellular signaling molecules, and gene expressions. We conclude that a,M and oM may function as specific neuroregulatory molecules in the rat nervous system, and the activated form of "2M may contribute to Alzheimer's disease if it accumulates in the brain. (NIH Grant NS-30698).

Original languageEnglish (US)
Pages (from-to)A973
JournalFASEB Journal
Issue number9
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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