Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Química Encefálica , Precursores de Proteínas/genética , Neoplasias das Glândulas Suprarrenais/patologia , Doença de Alzheimer/metabolismo , Sequência de Aminoácidos , Peptídeos beta-Amiloides/biossíntese , Precursor de Proteína beta-Amiloide , Sequência de Bases , Síndrome de Down/genética , Síndrome de Down/metabolismo , Regulação da Expressão Gênica , Genes , Humanos , Dados de Sequência Molecular , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/toxicidade , Feocromocitoma/patologia , Precursores de Proteínas/biossíntese , Processamento de Proteína Pós-Traducional , RNA Mensageiro/biossíntese , Proteínas Recombinantes/toxicidade , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Amyloid deposition in senile plaques and the cerebral vasculature is a marker of Alzheimer's disease. Whether amyloid itself contributes to the neurodegenerative process or is simply a by-product of that process is unknown. Pheochromocytoma (PC12) and fibroblast (NIH 3T3) cell lines were transfected with portions of the gene for the human amyloid precursor protein. Stable PC12 cell transfectants expressing a specific amyloid-containing fragment of the precursor protein gradually degenerated when induced to differentiate into neuronal cells with nerve growth factor. Conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against the amyloid polypeptide. Thus, a peptide derived from the amyloid precursor may be neurotoxic.
Assuntos
Doença de Alzheimer/etiologia , Amiloide/fisiologia , Precursores de Proteínas/fisiologia , Doença de Alzheimer/patologia , Amiloide/genética , Northern Blotting , Linhagem Celular , Fibroblastos , Regulação da Expressão Gênica , Humanos , Immunoblotting , Neurônios/patologia , Hibridização de Ácido Nucleico , Feocromocitoma , Precursores de Proteínas/genética , RNA/análise , RNA/genética , Mapeamento por Restrição , Transfecção , Células Tumorais CultivadasRESUMO
An alternate form of the Alzheimer amyloid protein precursor mRNA that encodes a protease inhibitor domain has recently been reported. Oligonucleotide probes that differentiate between the two mRNAs are used to describe the expression of each amyloid precursor transcript in the human brain. RNA blot analyses show that one of the mRNAs is expressed selectively in the nervous system, that the two messages display different regional distributions in the adult human brain, and that the expression of the two mRNAs is differentially affected in Down's syndrome brain and in Alzheimer's disease frontal cortex. In situ hybridization shows that the two transcripts display the same laminar distribution in the adult cortex but that the transcripts differ significantly in their levels of expression in pyramidal cells of the hippocampus.