TABLE 7.
Summary of caspase-9 involvement in human degenerative pathologies.
| Disease | Tissue localization of pathologic Caspase-9 expression | Fluid Samples with Increased Caspase-9 | Strength of evidence | Summary of evidence linking caspase-9 with human pathology |
|---|---|---|---|---|
| Human pathologies associated with Caspase-9 loss of function | ||||
| Immunodeficiency/lymphoproliferation | -- | -- | Strong | —Functional human genetics |
| —Knockout mouse phenotype | ||||
| Neural tube defects | -- | -- | Strong | —Functional human genetics |
| —Knockout mouse phenotype | ||||
| Pediatric brain tumors (Li-Fraumeni-like syndrome) | -- | -- | Strong | —Functional human genetics |
| Human pathologies associated with increased Caspase-9 activity or expression | ||||
| Amyotrophic lateral sclerosis | Motor neurons | Serum | Moderate | —Therapeutic effect in animal models |
| —Correlation with disease severity | ||||
| Retinal detachment | Photoreceptors | Subretinal fluid | Moderate | —Therapeutic effect in animal models |
| —Correlation with disease severity | ||||
| Slow-Channel syndrome | Neuromuscular junctions | Moderate | —Therapeutic effect in animal models | |
| —Increased signal in patient samples | ||||
| Alzheimer’s disease | Neurons, neurofibrillary tangles | Platelet rich plasma | Weak | —Correlation with disease severity |
| Atherosclerosis | Aorta | -- | Weak | —Increased signal in patient samples |
| Behcet’s disease | Endothelial cells, neutrophils | -- | Weak | —Increased signal in patient samples |
| Cardiomyopathy | Myocardium | Serum | Weak | —Increased signal in patient samples |
| Cardioplegia | Myocardium | Blood | Weak | —Increased signal in patient samples |
| Chronic rejection of heart transplant | Myocardium | -- | Weak | —Correlation with disease severity |
| Diabetic retinopathy | Retinal ganglion neurons | -- | Weak | —Increased signal in patient samples |
| Glaucoma | Retinal ganglion neurons | -- | Weak | —Increased signal in patient samples |
| Huntington’s disease | Neurons, neuropil | CSF | Weak | —Correlation with disease severity |
| Multiple system atrophy | Neurons, oligodendrocytes, glia | -- | Weak | —Increased signal in patient samples |
| Sepsis | -- | Serum | Weak | —Correlation with disease severity |
| Traumatic brain injury | -- | CSF | Weak | —Correlation with disease severity |
| Lumbar disc disease | Cartilage, fibroblasts, inflammatory cells | -- | Weak | —Correlation with disease severity |
| —Genetic association studies | ||||
Summary of pathologies associated with either caspase-9 loss of function or upregulated caspase-9, and level of evidence implicating caspase-9 as a potential driver of disease pathology.