George T. Capone, M.D.
Research Scientist, Kennedy Krieger Institute Assistant Professor of Pediatrics at the Johns Hopkins University School of Medicine - Baltimore, MD
Trisomy 21 Research Conference
September 13-14, 2003. New Orleans, LA
  Reprinted with the permission of the author.

Mitochondia Inner Structure

What are Mitochondria?

Mitochondrial DNA

Mitochondrial Genetics

Mitochondria Energy Production

ATP Production

Mitochondrial ROS Production

ROS Production and Detoxification

Reactive Oxygen

Reactive Oxygen

Reactive Oxygen and Aging

Living to Die

Down Syndrome and Aging

Biomarkers for Oxidative Damage

Biomarkers for Oxidative Damage

DNA- oxidation and modification of nucleotide bases resulting in point mutation
8-Hydroxy-2-deoxyguanosine (8-OHdG)
Excision-repair cross complementing proteins (ERCC)

Evidence for Oxidative Damage in Living Persons with Down Syndrome

Evidence for Oxidative Damage in Down Syndrome Brain

Sources of ROS in Down Syndrome

Kennedy Krieger Study

GROUP   N   Age (mo)   Gender   IQ
46 48.1 (24.5) M=26
52 (13.4)
30   66.7* (17.4)   M=20
50 (19/7)
Controls 43 49.3 (25.6) M=22
  103** (12/7)  

Research Protocol

Mitochondrial Superoxide Detection

Mitochondrial Superoxide Detection

Superoxide Production Group Comparison

Total and Peak LDCL levels by Group

Biomarkers of Superoxide & Lipid Peroxidation

    LDCL peak     Lipid peroxides   TBARS IQ
0.74* (0.52) 5.19 (9.3)   0.20 (0.13)   52.1 (13.5)
0.54 (0.48) 7.28 (11.34) 0.18 (0.15) 49.6 (19.7)
Controls 0.47 (0.41) 3.7 (4.83) 0.16 (0.10)   103.4* (12.4)  

Mitochondrial Dysfunction in Down Syndrome?

The Vulnerable Brain

Lipid Peroxidation of Neuronal Membranes

Lipid Peroxidation of Neuronal Membranes

Implications for Cognitive & Mental Health

Possible Therapeutics for Mitochodrial Energy Dysfunction

Future Directions