Apoptotic death induces Abeta production and fibril formation to a much larger extent than necrotic-like death in CGNs.
In this study we report that apoptotic death of primary cultures of cerebellar granule neurons is accompanied by release of thioflavin-binding proteins - indicative of the presence of beta-sheet structures - and fibril formation in the culture medium. When the same neurons are subjected to an excytotoxic death caused by 100 microM glutamate exposure, the amount of thioflavin binding is markedly reduced. Western blot analysis shows that fibrils contain monomers, dimers and trimers of amyloid-beta (Abeta) which, when observed at the electron microscope, have morphologies reminiscent of fibrils of senile plaques. These findings demonstrate that triggering an apoptotic pathway leads to beta-sheet transition and fibril formation of a protein primarily involved in Alzheimer's disease and may be of direct relevance to the possible link between apoptosis and this neuropathology.
Cicconi
Simona
S
Institute of Neurobiology and Molecular Medicine, CNR, Roma and European Brain Research Institute EBRI, Roma, Italy.
Gentile
Antonietta
A
Ciotti
Maria Teresa
MT
Parasassi
Tiziana
T
Serafino
Annalucia
A
Calissano
Pietro
P
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D017209:Apoptosis / Q000502:physiology*; D052160:Benzothiazoles; D002531:Cerebellum / Q000473:pathology; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D009336:Necrosis / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D012155:Reticulin / Q000096:biosynthesis* / Q000648:ultrastructure; D013844:Thiazoles
D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; C061407:CGN protein, human; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D008840:Microfilament Proteins; D012155:Reticulin; D013844:Thiazoles; C009462:thioflavin T