The mechanism of -amyloid peptide influence on the retrograde axon transport
M A Mukhamed'yarov , Z Z Safiullov , R P Utyasheva , A A Rizvanov , A L Zefirov , R R Islamov , M A Mukhamedyarov , Z Z Safiullov , R P Utyasheva , A A Rizvanov , A L Zefirov , R R Islamov
Genes & Cells ›› 2012, Vol. 7 ›› Issue (3) : 135 -137.
The mechanism of -amyloid peptide influence on the retrograde axon transport
Impairment of axon transport is widespread and earlyevent in a number of neurodegenerative diseases. The goalof study is to investigate the mechanisms of retrograde axontransport impairment in mouse spinal motoneurons afterapplication of -amyloid peptide (AP) (25-35) on the centralstump of transected sciatic nerve.Retrograde fluorescent tracer Fluorogold (5%), AP(25-35) (10-6 М), or mix was applied to the proximal stumpof the transected sciatic nerve of mouse under the generalanesthesia. At 24 hours after surgery lumbar spinal cordwas processed for morphometric and immunohistochemicalanalysis.The amount of Fluorogold-positive motoneurons at controlwas 1223,7162,7 (n = 7), whereas after application ofAP(25-35) - 393,285,3 (n = 5, p < 0,01), which certifiespronounced inhibition of retrograde axonal transport. Stainingwith polyclonal antibodies against caspase-3 did not revealmotoneurons in apoptotic state. Staining with monoclonalantibodies against the AP (25-35) was negative both atoperated and intact sides of spinal cord.Thus, revealed inhibitory action of AP (25-35) on theretrograde axon transport is not related to apoptotic death ofneurons or accumulation of AP (25-35) inside the neuronalsoma, but, evidently, is mediated by intraaxonal effects.Obtained data has great importance for understanding ofmechanisms of Alzheimers disease pathogenesis.
-amyloid peptide / Alzheimer's disease / retrograde axon transport / motoneuron / caspase-3
| [1] |
De Vos K.J., Grierson A.J., Ackerley S. et al. Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci. 2008; 31: 151-73. |
| [2] |
Morfini G.A., Burns M., Binder L.I. et al. Axonal transport defects in neurodegenerative diseases. J. Neurosci. 2009; 29(41): 12776-86. |
| [3] |
Stokin G.B., Lillo C., Falzone T.L. et al., Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 2005; 307(5713): 1282-8. |
| [4] |
Lazarov O., Morfini G.A., Pigino G. et al. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J. Neurosci. 2007; 27(26): 7011-20. |
| [5] |
Querfurth H.W., LaFerla F.M. Alzheimer's disease. N. Engl. J. Med. 2010; 362(4): 329-44. |
| [6] |
Kamada S., Kikkawa U., Tsujimoto Y. et al. Nuclear translocation of caspase-3 is dependent on its proteolytic activation and recognition of a substrate-like protein(s). J. Biol. Chem. 2005; 280(2): 857-60. |
| [7] |
Zheng T.S., Schlosser S.F., Dao T. et al. Caspase-3 controls both cytoplasmic and nuclear events associated with Fas-mediated apoptosis in vivo. PNAS USA 1998; 95(23): 13618-23. |
| [8] |
Woo M., Hakem R., Soengas M.S. et al. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 1998; 12(6): 806-19. |
| [9] |
Bayer T.A., Wirths O. Intracellular accumulation of amyloid-Beta - a predictor for synaptic dysfunction and neuron loss in Alzheimer's disease. Front Aging Neurosci. 2010; 2: 8. |
Eco-Vector
/
| 〈 |
|
〉 |
PDF
