Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 16, Issue 3, Pages 585-599Publisher
IOS PRESS
DOI: 10.3233/JAD-2009-0995
Keywords
Central nervous system; dementia with Lewy bodies; human; insulin-like growth factor resistance; neurotrophin; Parkinson's disease; receptor-ligand binding
Categories
Funding
- Neuropathology Core of the Massachusetts ADRC [P50 AG005134]
- National Institute on Aging/National Institutes of Health [P50AG05128]
- [AA-11431]
- [AA-12908]
- [K24 AA-15926]
- NATIONAL INSTITUTE ON AGING [P50AG005134, P50AG005128] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R37AA011431, R56AA011431, R01AA012908, K24AA016126, R01AA011431] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) frequently overlap with Alzheimer's disease, which is linked to brain impairments in insulin, insulin-like growth factor (IGF), and neurotrophin signaling. We explored whether similar abnormalities occur in PD or DLB, and examined the role of manganese toxicity in PD/DLB pathogenesis. Quantitative RT-PCR demonstrated reduced expression of insulin, IGF-II, and insulin, IGF-I, and IGF-II receptors ( R) in PD and/ or DLB frontal white matter and amygdala, and reduced IGF-IR and IGF-IIR mRNA in DLB frontal cortex. IGF-I and IGF-II resistance was present in DLB but not PD frontal cortex, and associated with reduced expression of Hu, nerve growth factor, and Trk neurotrophin receptors, and increased levels of glial fibrillary acidic protein, alpha-synuclein, dopamine-beta-hydroxylase, 4-hydroxy-2-nonenal (HNE), and ubiquitin immunoreactivity. MnCl2 treatment reduced survival, ATP, and insulin, IGF-I and IGF-II receptor expression, and increased alpha-synuclein, HNE, and ubiquitin immunoreactivity in cultured neurons. The results suggest that: 1) IGF-I, IGF-II, and neurotrophin signaling are more impaired in DLB than PD, corresponding with DLB's more pronounced neurodegeneration, oxidative stress, and alpha-synuclein accumulation; 2) MnCl2 exposure causes PD/DLB associated abnormalities in central nervous system neurons, and therefore may contribute to their molecular pathogenesis; and 3) molecular abnormalities in PD/DLB overlap with but are distinguishable from Alzheimer's disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available