Table 3.

Cathepsin B gene deletion improves deficits of TBI and TBI-related animal models.

Model	Cathepsin B gene deletion effect			Reference
	Behavior	Pathology	Biomarkers
Trauma TBI	↓ Neuromotor dysfunction	Brain ↓ Lesion vol; Neuron death	↓ Brain bax	(48)
Trauma surgery post-op ileus	nd	↓ ECM destruction	↓ ECM collagen IV	(101)
Neuroexcitatory epilepsy	No effect on seizures	↓ Brain neuron death	nd	(138)
Neurodegeneration AD transgenic human APPwt	nd	nd	Brain ↓ Aβ (1-40/42); CTFβ ↑ sAPPα	(139)
Neurodegeneration disease AD transgenic human APPLon	↓ Memory deficits	↓ Brain Aβ plaque	Brain ↓ Aβ(1-40/42); CTFβ ↑ sAPPα	(140)
		↓ Brain pGlu-Aβ plaque	↓ Brain pGlu-Aβ(3-40/42)	(141)
Neurodegeneration AD transgenic human APPSwe	nd	↑ Brain plaque	No significant change brain Aβ (1-X/42)	(142)
Neurodegeneration fibrial Aβ, chromogranin microglia challenge	nd	nd	↓ microglia IL-1β, caspase 1	(143)
Inflammation/pain	↓ Chronic inflammatory pain	↓ Activated microglia	Brain ↓ mIL-1β; mIL-18; Cox2	(115)
Aging inflammation	nd	nd	↓ Brain IL-1β	(116)
LPS-induced inflammation	nd	nd	Macrophages ↓ TNFα secretion	(144)
TNFα challenged hepatocytes	nd	nd	Hepatocytes ↓ caspase 2 ↓ mito cyt c	(145)
Neuro-degeneration MS EAE cathepsin B and S double knockout	nd	Improved clinical score ↓ spinal cord leukocyte infiltration ↑ age of onset	↓ Immune cell markers (MHC-II, CD69 CD4+ cells)	(146)

nd, not done; ECM, extracellular matrix; mIL-1β, mature interleukin-1β; mIL-18, mature interleukin-18β; mito cyt c, mitochondrial cytochrome c; ALT, alanine aminotransferase; HSC, hepatic stellar cells; APPwt, wild-type amyloid precursor protein; APPLon, amyloid precursor protein containing the London mutation, CTFβ, C-terminal β-secretase fragment; pyrogluAβ, pyroglutamate Aβ; EAE, experimental autoimmune encephalomyelitis. Blue and tan colors indicate significant effects on behavior and pathology, respectively, by cathepsin B gene deletion.