Neuronal specific targeting of caveolin expression to restore synaptic signaling and improve cognitive function in the neurodegenerative brain and motor function in spinal cord
The invention provides an expression system for producing Caveolin-1 in neuronal cells or neural stem cells comprising a neuron-specific regulatory element and a nucleic acid sequence encoding Caveolin-1.
1. A method of transferring the caveolin-1 gene into a neural stem cell or neuronal cell comprising introducing an expression system into the neural stem cell or neuronal cell, thereby transferring the caveolin-1 gene into a neural stem cell or neuronal cell, respectively; wherein the expression system for producing Caveolin-1 in neuronal cells or neural stem cells comprises:
(a) a neuron-specific regulatory element; and
(b) a nucleic acid sequence encoding Caveolin-1,
wherein the neuron-specific regulatory element of (a) is a promoter and located upstream of the nucleic acid sequence encoding Caveolin-1 of (b) and directs the expression of Caveolin-1 in the neural stem cell or neuronal cell.
2. The method of claim 1 , wherein the nucleic acid sequence encoding Caveolin-1 is set forth in SEQ ID NO:1 beginning at position 568 and ending at position 1104.
3. The method of claim 1 , wherein the nucleic acid sequence encoding Caveolin-1 is set forth in SEQ ID NO:5 beginning at position 1 and ending at position 537.
4. The method of claim 1 , wherein the nucleic acid sequence encoding Caveolin-1 is set forth in SEQ ID NO:7 beginning at position 1 and ending at position 537.
5. The method of claim 1 , wherein the neuron-specific regulatory element is the synapsin promoter as set forth in FIG. 8 (SEQ ID NO:1) beginning at position 21 and ending at position 489.
6. A method for promoting neural cell growth comprising transforming an expression system comprising (a) a neuron-specific regulatory element; and (b) a nucleic acid sequence encoding Caveolin-1 into a neuronal cells, wherein the neuron-specific regulatory element of (a) is a promoter and located upstream of the nucleic acid sequence encoding Caveolin-1 of (b) and directs the expression of Caveolin 1 in the neural cells in a sufficient amount so as to promote neural cell growth.
7. A method of increasing synapse formation and improving synaptic function in neurodegenerative diseases by promoting neural cell growth in a subject by the method of claim 6 , thereby increasing synapse formation and improving synaptic function.
8. The method of claim 7 , wherein the neurodegenerative disease is Alzheimer's Disease.