Lead (Pb) exposure and its effect on APP proteolysis and A beta aggregation
Basha, MR; Murali, M; Siddiqi, HK; Ghosal, K; Siddiqi, OK; Lashuel, HA; Ge, YW; Lahiri, DK; Zawia, NH
HERO ID
451747
Reference Type
Journal Article
Year
2005
Language
English
PMID
| HERO ID | 451747 |
|---|---|
| In Press | No |
| Year | 2005 |
| Title | Lead (Pb) exposure and its effect on APP proteolysis and A beta aggregation |
| Authors | Basha, MR; Murali, M; Siddiqi, HK; Ghosal, K; Siddiqi, OK; Lashuel, HA; Ge, YW; Lahiri, DK; Zawia, NH |
| Journal | FASEB Journal |
| Volume | 19 |
| Issue | 14 |
| Page Numbers | 2083-2084 |
| Abstract | Alzheimer's disease ( AD) is a progressive neurodegenerative disorder with clinical manifestations appearing in old age, however, the initial stages of this disease may begin early in life. AD is characterized by the presence of excessive deposits of aggregated beta-amyloid ( A beta) peptides, which are derived from the beta-amyloid precursor protein ( APP) following processing by beta-secretase and gamma-secretase. Recently, we have reported that developmental exposure of rats to Pb resulted in latent elevation of APP mRNA, APP, and A beta in old age. Here we examined whether latent up-regulation in APP expression and A beta levels is exacerbated by concurrent disturbances in APP processing or A beta aggregation. Among the environmental metals tested, only A beta solutions containing Pb promoted the formation of A beta aggregates at nanomolar concentrations. The lifetime profiles of alpha-, beta-, and gamma-secretases remained constant in adult and aging animals, and developmental exposure to Pb did not alter them. Furthermore, the addition of various concentrations of Pb ( 0.1 to 50 mu M) to cerebral cortical extracts derived from control animals also did not affect the proteolytic activities of these enzymes. Therefore, we propose that amyloidogenesis is promoted by a latent response to developmental reprogramming of the expression of the APP gene by early exposure to Pb, as well as enhancement of A beta aggregation in old age. In rodents, these events occur without Pb-induced disturbances to the enzymatic processing of APP. The aforementioned results provide further evidence for the developmental basis of amyloidogenesis and late-life disturbances in AD-associated proteins by environmental agents. |
| Doi | 10.1096/fj.05-4375fje |
| Pmid | 16230335 |
| Wosid | WOS:000232991100016 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
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