| title: | Mitochondrial-aconitase dysfunction in aging and degenerative brain: mechanisms and therapeutic possibilities |
|---|---|
| reg no: | ETF6574 |
| project type: | Estonian Science Foundation research grant |
| subject: |
3.1. Basic Medicine |
| status: | accepted |
| institution: | TU Faculty of Medicine |
| head of project: | Ello Karelson |
| duration: | 01.01.2006 - 31.12.2009 |
| description: | The planned project represents a development of previous results and aims mainly at elucidation the dysfunction mechanism for the Krebs cycle energetically critical enzyme Fe-dependent mitochondrial aconitase (m-acon) in brain aging and degeneration (particularly in Alzheimer's disease, AD). The concrete study-aims are as follows: 1)to find out the post-mortal relationship between the m-acon activity and human age in different brain regions of normally aging persons and of patients with sporadic and Swedish Familial AD; 2)to elucidate the m-acon dysfunction mechanisms in different model systems (mitochondria of postmortal brain and cultured nerve cells, in situ model of nerve cells); 3)to elucidate the mitochondrial mechanisms for reactive oxygen and nitrogen species, pro-oxidative metabolites and amyloid-beta peptides that might lead to the m-acon damage and dysfunction; 4)to estimate the age-dependent activity and immunohistochemical parameters for mitochondrial protector enzymes(MnSOD, GSHPx) in the aging and AD brain regions; to elucidate the m-acon re-activating mechanisms for low-molecular neuroptocetors (incl. drugs), particularly for Fe-chelators, NOS-inhibitors and MnSOD-mimickers. The results might be applied for decelerating the brain mitochondrial aging and reducing the risk of neurodegeneration. The results would assist to slower the subclinical and early-stage progression of neurodegenerative diseases, particularly of AD. The study would contribute to the purposeful synthesis of novel and effective neuroprotectants. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Nenad Bogdanovic | |||
| 2. | Viktor Jefremov | |||
| 3. | Ceslava Kairane | |||
| 4. | Ello Karelson | Tartu Ülikool | ||
| 5. | Tiit Land | |||
| 6. | Aune Rehema | |||
| 7. | Kristiina Roots | |||
| 8. | Helle-Evi Simovart | |||
| 9. | Külli Teder | |||