angiogenin and Parkinsonian-Disorders

Parkinson's disease (PD) is the second most common form of neurodegeneration among the elderly population. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. Interestingly, a significant association has been demonstrated between PD and low levels of vitamin D in the serum, and vitamin D supplement appears to have a beneficial clinical effect on PD. Genetic studies have provided the opportunity to determine which proteins link vitamin D to PD pathology, e.g., Nurr1 gene, toll-like receptor, gene related to lipid disorders, vascular endothelial factor, tyrosine hydroxylase, and angiogenin. Vitamin D also exerts its effects on cancer through nongenomic factors, e.g., bacillus Calmette-Guerin vaccination, interleukin-10, Wntβ-catenin signaling pathways, mitogen-activated protein kinase pathways, and the reduced form of the nicotinamide adenine dinucleotide phosphate. In conclusion, vitamin D might have a beneficial role in PD. Calcitriol is best used for PD because it is the active form of the vitamin D(3) metabolite and modulates inflammatory cytokine expression. Further investigation with calcitriol in PD is needed.

Topics: Animals; BCG Vaccine; Calcitriol; Cholesterol; Genetic Association Studies; Humans; Hypercalcemia; Mice; Mice, Knockout; NADPH Oxidases; Nuclear Receptor Subfamily 4, Group A, Member 2; Parkinson Disease; Parkinsonian Disorders; Rats; Receptors, Calcitriol; Ribonuclease, Pancreatic; Signal Transduction; Toll-Like Receptors; Tyrosine 3-Monooxygenase; Vascular Endothelial Growth Factor A; Vitamin D; Vitamin D Deficiency

We previously observed marked down-regulation of the mRNA for angiogenin, a potent inducer of neovascularization, in a mouse model of Parkinson's disease (PD) based on over-expression of alpha-synuclein. Angiogenin has also been recently implicated in the pathogenesis of amyotrophic lateral sclerosis. In this study, we confirmed that mouse angiogenin-1 protein is dramatically reduced in this transgenic alpha-synuclein mouse model of PD, and examined the effect of angiogenin in cellular models of PD. We found that endogenous angiogenin is present in two dopamine-producing neuroblastoma cell lines, SH-SY5Y and M17, and that exogenous angiogenin is taken up by these cells and leads to phosphorylation of Akt. Applied angiogenin protects against the cell death induced by the neurotoxins 1-methyl-4-phenylpyridinium and rotenone and reduces the activation of caspase 3. Together our data supports the importance of angiogenin in protecting against dopaminergic neuronal cell death and suggests its potential as a therapy for PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Cell Death; Cell Line, Tumor; Cytoprotection; Disease Models, Animal; Dopamine; Humans; Mice; Mice, Knockout; Mice, Transgenic; Nerve Degeneration; Neuroblastoma; Neuroprotective Agents; Oncogene Protein v-akt; Parkinsonian Disorders; Phosphorylation; Ribonuclease, Pancreatic