Treatment of neurodegenerative diseases using proteasome modulators
Methods for modulating proteasome activity in a subject is provided. Proteasome activity is modulated by administering a therapeutically effective amount of proteasome modulating pharmacological agent to a subject. In a preferred embodiment, the proteasome modulating pharmacological agent is a protease inhibitor. In another aspect, a screening assay for detecting and identifying proteasome modulating pharmacological agents to modulate proteasome activity in a subject is also provided.
1. A method of assessing whether a subject is afflicted with a neurodegenerative disease selected from the group consisting of Amyotrophic Lateral Sclerosis (ALS), multiple sclerosis, Huntington's disease, Parkinson's disease, prion associated disease, spinal muscular atrophy, spinal cerebellar ataxia, and spinal cord injury, the method comprising, comparing:
the level of proteasome activity in a test sample from a subject, by measuring the expression levels in the test sample of at least one proteasome subunit selected from the group consisting of LMP-2, LMP-7 and MECL-1, and
a normal level of proteasome activity for said at least one proteasome subunit,
wherein a significant difference between the level of proteasome activity in the test sample and the normal level is an indication that the subject is afflicted with a neurodegenerative disease.
2. The method of claim 1 , wherein the proteasome subunit is LMP-2.
3. The method of claim 1 , wherein the proteasome subunit is LMP-7.
4. The method of claim 1 , wherein the proteasome subunit is MECL-1.
5. A method of assessing whether a subject is afflicted with Amyotrophic Lateral Sclerosis (ALS), the method comprising,
measuring the expression level of at least one proteasome subunit selected from the group consisting of LMP-2, LMP-7 and MECL-1 in a test sample from a subject, and
comparing the measured level with a normal level wherein a significant difference between the measured level and the normal level is an indication that the subject is afflicted with a Amyotrophic Lateral Sclerosis.
6. The method of claim 5 , wherein the proteasome subunit is LMP-2.
7. The method of claim 5 , wherein the proteasome subunit is LMP-7.
8. The method of claim 5 , wherein the proteasome subunit is MECL-1.
9. The method of claim 5 , wherein elevated levels of LMP-2, LMP-7 or MECL-1 in a test sample indicates that the subject is afflicted with amyotrophic Lateral Sclerosis (ALS).
10. A method of assessing whether a subject is at risk for developing Amyotrophic Lateral Sclerosis (ALS), the method comprising,
measuring the expression level of at least one proteasome subunit in a test sample from a subject, and
comparing the measured level with a normal level, wherein a significant difference between the measured level and the normal level is an indication that the subject is at risk for developing ALS.
11. The method of claim 10 , wherein the proteasome subunit is selected from the group consisting of LMP-2, LMP-7 and MECL-1.
12. The method of claim 10 , wherein elevated levels of at least one of LMP-2, LMP-7 or MECL-1 in a test sample indicates that the subject is at risk for developing ALS.