RESUMO
Glial fibrillary acidic protein (GFAP) is considered to be a highly specific marker for glia. Here, we report on the expression of GFAP in neurons in the human hippocampus. Intriguingly, this neuronal GFAP is coded by out-of-frame splice variants and its expression is associated with Alzheimer pathology. We identified three novel GFAP splice forms: Delta 135 nt, Delta exon 6 and Delta 164 nt. Neuronal GFAP is mainly observed in the pyramidal neurons of the hippocampus of Alzheimer and Down syndrome patients and aged controls, but not in neurons of patients suffering from hippocampal sclerosis. Apparently, the hippocampal neurons in patients with Alzheimer's disease pathology are capable of expressing glia-specific genes.
Assuntos
Processamento Alternativo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Mudança da Fase de Leitura do Gene Ribossômico , Proteína Glial Fibrilar Ácida/metabolismo , Neurônios/metabolismo , Transcrição Gênica , Doença de Alzheimer/genética , Sequência de Aminoácidos , Sequência de Bases , Síndrome de Down/genética , Síndrome de Down/metabolismo , Síndrome de Down/patologia , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Éxons , Feminino , Proteína Glial Fibrilar Ácida/genética , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Dados de Sequência Molecular , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/patologia , RNA Mensageiro/análise , Fases de Leitura/genética , EscleroseRESUMO
+1 Frame-shifted proteins such as amyloid precursor protein(+1) and ubiquitin-B(+1) have been identified in the neuropathological hallmarks of Alzheimer's disease. These frameshifts are caused by dinucleotide deletions in GAGAG motifs of messenger RNA encoded by genes that have maintained the unchanged wild-type DNA sequence. This process is termed 'molecular misreading'. A key question is whether this process is confined to neurons or whether it could also occur in non-neuronal cells. A transgenic mouse line (MV-B) carrying multiple copies of a rat vasopressin minigene as a reporter driven by the MMTV-LTR promotor was used to screen non-neuronal tissues for molecular misreading by means of detection of the rat vasopressin(+1) protein and mutated mRNA. Molecular misreading was demonstrated to occur in several organs (e.g., epididymis and the parotid gland) where transgenic vasopressin expression is abundant, but its penetrance is variable both between and within tissues. This implies that non-neural tissues too, could be affected by cellular derangements caused by molecular misreading.
