Compositions and methods for treating neurodegenerative disroders
A method of inhibiting aberrant ATAD3A activation and/or oligomerization in mitochondria of a cell includes administering to the cell a therapeutic agent that inhibits binding or complexing of ATAD3A with Drp1 in the mitochondria of the cell.
1. A method of inhibiting aberrant ATPase family AAA-domain containing protein 3A (ATAD3A) activation and/or oligomerization in mitochondria of a cell, the method comprising:
administering to the cell a therapeutic peptide linked to a transport moiety, wherein
the therapeutic peptide consists of about 6 to about 12 amino acids and has at least about 80% sequence identity to about 6 to about 12 consecutive amino acids of an interaction site of dynamin-related protein 1 (Drp1) with a first coiled-coil domain of ATAD3A, and inhibits binding or complexing of ATAD3A with Drp-1 in the mitochondria of the cell; and
wherein the transport moiety facilitates uptake of the therapeutic peptide by a nerve cell.
2. The method of claim 1 , wherein the cell is a nerve cell of a subject with a neurodegenerative disorder.
3. The method of claim 1 , wherein the therapeutic peptide has an amino acid sequence that is at least about 80% identical to at least 6 consecutive amino acids of SEQ ID NO: 1.
4. The method of claim 3 , wherein the therapeutic peptide has an amino acid sequence at least 80% identical to SEQ ID NO: 2.
5. The method of claim 1 , wherein the transport moiety is an HIV Tat transport moiety.
6. The method of claim 1 , wherein the cell is a nerve cell in a subject with neurodegenerative disorder and the therapeutic peptide is administered systemically to the subject.
7. The method of claim 1 , wherein the therapeutic peptide has the amino acid sequence of SEQ ID NO: 2 and is linked to a HIV Tat transport moiety.
8. A method of treating a disorder associated with aberrant ATAD3A activation in mitochondria of nerves cells in a subject in need thereof, the method comprising:
administering to the subject
a therapeutic peptide linked to a transport moiety, wherein the therapeutic peptide consists of about 6 to about 12 amino acids and has at least about 80% sequence identity to about 6 to about 12 consecutive amino acids of an interaction site of Drp1 with a first coiled-coil domain of ATAD3A, and inhibits binding of ATAD3A with Drp1 in the mitochondria of the nerve cells, and
wherein the transport moiety facilitates uptake of the therapeutic peptide by the nerve cell.
9. The method of claim 8 , wherein the disorder is a neurodegenerative disorder.
10. The method of claim 8 , wherein the disorder is Huntington's disease.
11. The method of claim 8 , wherein the therapeutic peptide has an amino acid sequence that is at least about 80% identical to at least 6 consecutive amino acids of SEQ ID NO: 1.
12. The method of claim 11 , wherein the therapeutic peptide has an amino acid sequence at least 80% identical to SEQ ID NO: 2.
13. The method of claim 8 , wherein the transport moiety is an HIV Tat transport moiety.
14. The method of claim 8 , wherein the therapeutic peptide is administered systemically to the subject.
15. The method of claim 8 , wherein the therapeutic peptide has the amino acid sequence of SEQ ID NO: 2 and is linked to a HIV Tat transport moiety.
16. The method of claim 8 , wherein the therapeutic peptide and the transport moiety together have the amino acid sequence of SEQ ID NO: 16.