RGD Reference Report - Brain insulin-like growth factor and neurotrophin resistance in Parkinson's disease and dementia with Lewy bodies: potential role of manganese neurotoxicity. - Rat Genome Database

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Brain insulin-like growth factor and neurotrophin resistance in Parkinson's disease and dementia with Lewy bodies: potential role of manganese neurotoxicity.

Authors: Tong, M  Dong, M  De la Monte, SM 
Citation: Tong M, etal., J Alzheimers Dis. 2009;16(3):585-99.
RGD ID: 5129515
Pubmed: PMID:19276553   (View Abstract at PubMed)
PMCID: PMC2852260   (View Article at PubMed Central)
DOI: DOI:10.3233/JAD-2009-0995   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Lewy body dementia  IDA 5129515 RGD 
Lewy body dementia  IEP 5129515mRNA:altered expression:brain:RGD 
Lewy body dementia  IEP 5129515mRNA:decreased expression:frontal cortexRGD 
Lewy body dementia  ISOIGF1R (Homo sapiens)5129515; 5129515mRNA:altered expression:brain:RGD 
Lewy body dementia  ISOIGF2 (Homo sapiens)5129515; 5129515mRNA:decreased expression:frontal cortexRGD 
Parkinson's disease  IEP 5129515protein:increased expression:frontal cortex (human)RGD 
Parkinson's disease  ISODBH (Homo sapiens)5129515; 5129515protein:increased expression:frontal cortex (human)RGD 
Parkinson's disease  IEP 5129515mRNA:altered expression:brain:RGD 
Parkinson's disease  IEP 5129515mRNA:decreased expression:frontal cortexRGD 
Parkinson's disease  ISOIGF1R (Homo sapiens)5129515; 5129515mRNA:altered expression:brain:RGD 
Parkinson's disease  ISOIGF2 (Homo sapiens)5129515mRNA:decreased expression:frontal cortexRGD 
Parkinson's disease  ISOIGF2 (Homo sapiens)5129515mRNA:decreased expression:frontal cortex:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to manganese ion  IEP 5129515 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dbh  (dopamine beta-hydroxylase)
Igf1r  (insulin-like growth factor 1 receptor)
Igf2  (insulin-like growth factor 2)

Genes (Mus musculus)
Dbh  (dopamine beta hydroxylase)
Igf1r  (insulin-like growth factor I receptor)
Igf2  (insulin-like growth factor 2)

Genes (Homo sapiens)
DBH  (dopamine beta-hydroxylase)
IGF1R  (insulin like growth factor 1 receptor)
IGF2  (insulin like growth factor 2)

Objects referenced in this article
Gene IGF1 insulin like growth factor 1 Homo sapiens
Gene Igf1 insulin-like growth factor 1 Mus musculus
Gene Igf1 insulin-like growth factor 1 Rattus norvegicus

Additional Information