Akt signal transduction dysfunction in Parkinson's disease Export

@article{citeulike:5907378, abstract = {Significant attention has been drawn to the potential role of defective PI3-kinase-Akt (PKB) signalling in Parkinson's disease (PD) neurodegeneration and to the possibility that activation of Akt may provide neuroprotection in PD. However, little knowledge exists on the integrity of the Akt system in PD. Results of the present study show diminished levels of both total and active phospho Ser473 -Akt in the brain in PD. This was evident by western blot analysis of midbrain fractions from PD compared to non-PD control brain, but more specifically by immunofluorescence microscopy of the substantia nigra pars compacta (SNpc). Here, double immunofluorescence microscopy found Akt and phospho Ser473 -Akt to be expressed at high levels in tyrosine hydroxylase (TH) immunopositive dopaminergic neurons in control human brain. Selective loss of these neurons was accompanied by a marked decrease of Akt and phospho Ser473 -Akt expression in the PD brain, however Akt and active phospho Ser473 -Akt are still evident in degenerating dopaminergic neurons in the disease. This suggests that it may be possible to target neuronal Akt in advanced PD. Converse to the marked loss of neuronal Akt in PD, increased Akt and phospho Ser473 -Akt levels were observed in small non-TH positive cells in PD SNpc, whose increased number and small nuclear size indicate they are glia. These findings implicate defective Akt as a putative signalling pathway linked to loss of dopaminergic neurons in PD.}, author = {Timmons, Suzanne and Coakley, Meghan F. and Moloney, Aileen M. and O' Neill, Cora}, citeulike-article-id = {5907378}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.neulet.2009.09.055}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S030439400901283X}, day = {01}, doi = {10.1016/j.neulet.2009.09.055}, issn = {03043940}, journal = {Neuroscience Letters}, keywords = {antibdoy, antibody, blot, disease, enolase, neuron, nse, parkinsons, specific, tuj-1, western}, month = {October}, posted-at = {2009-10-15 16:11:06}, priority = {0}, title = {Akt signal transduction dysfunction in Parkinson's disease}, url = {http://dx.doi.org/10.1016/j.neulet.2009.09.055}, year = {2009} }

TY - JOUR ID - citeulike:5907378 L3 - citeulike-article-id:5907378 N2 - Significant attention has been drawn to the potential role of defective PI3-kinase-Akt (PKB) signalling in Parkinson's disease (PD) neurodegeneration and to the possibility that activation of Akt may provide neuroprotection in PD. However, little knowledge exists on the integrity of the Akt system in PD. Results of the present study show diminished levels of both total and active phospho Ser473 -Akt in the brain in PD. This was evident by western blot analysis of midbrain fractions from PD compared to non-PD control brain, but more specifically by immunofluorescence microscopy of the substantia nigra pars compacta (SNpc). Here, double immunofluorescence microscopy found Akt and phospho Ser473 -Akt to be expressed at high levels in tyrosine hydroxylase (TH) immunopositive dopaminergic neurons in control human brain. Selective loss of these neurons was accompanied by a marked decrease of Akt and phospho Ser473 -Akt expression in the PD brain, however Akt and active phospho Ser473 -Akt are still evident in degenerating dopaminergic neurons in the disease. This suggests that it may be possible to target neuronal Akt in advanced PD. Converse to the marked loss of neuronal Akt in PD, increased Akt and phospho Ser473 -Akt levels were observed in small non-TH positive cells in PD SNpc, whose increased number and small nuclear size indicate they are glia. These findings implicate defective Akt as a putative signalling pathway linked to loss of dopaminergic neurons in PD. JF - Neuroscience Letters SN - 03043940 TI - Akt signal transduction dysfunction in Parkinson's disease KW - antibdoy KW - antibody KW - blot KW - disease KW - enolase KW - neuron KW - nse KW - parkinsons KW - specific KW - tuj-1 KW - western AU - Timmons, Suzanne AU - Coakley, Meghan AU - Moloney, Aileen AU - O’ Neill, Cora PY - 2009/10/01/ UR - http://dx.doi.org/10.1016/j.neulet.2009.09.055 ER -