[Abeta, tau and alpha-synuclein and glial cells].
Many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are now characterized by abnormal accumulation of certain proteins in the brain. The key molecules include amyloid beta-protein (Abeta), tau and a-synuclein, all of which are involved in the pathogenesis and provide histopathological hallmarks of the diseases. Abeta is continuously produced in and removed from the brain. Microglia and astrocytes take up and degrade soluble Abeta. In the Alzheimer brain, once-deposited, insoluble Abeta is also removed by phagocytosis by activated microglia. The success of these removal processes, however, is at best partial. The phagocytic removal of insoluble Abeta is associated with neuroinflammation, a potentially neurotoxic reaction. Tau is accumulated in astrocytes under a diversity of pathological conditions in several forms: thorn-shaped astrocytes; tuft-shaped astrocytes; astrocytic plaques. Thorn-shaped astrocytes are associated with gliosis and are not disease-specific. Tuft-shaped astrocytes are characteristic of progressive supranuclear palsy (PSP) and astrocytic plaques of cortico-basal degeneration (CBD). Tau accumulation in oligodendrocytes is referred to as coiled bodies and occurs in PSP, CBD, Pick's disease and some other so-called taupathies. a-Synuclein is accumulated in oligodendrocytes, which is referred to as glial cytoplasmic inclusions (GCI). Occurrence of GCI is diagnostic to multiple system atrophy. Transgenic mouse models in which tau or alpha-synuclein is overexpressed in glial cells indicate that neuronal degeneration occurs following tau/alpha-synuclein accumulation in glial cells, supporting a notion that these abnormal glial cells play pathogenic roles.
Akiyama
Haruhiko
H
Tokyo Institute of Psychiatry, Japan. akiyama@prit.go.jp
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins