Table 3.

Chemical inhibition of cathepsin B improves behavioral dysfunction and neuropathology in AD, TBI, and related animal models

Disease Model	Inhibitor (route)	Behavior	Pathology	Biomarkers	Refs.
AD APPLon	E64d (oral) E64d (icv) CA-074Me (icv)	↓ memory deficits	↓ amyloid plaque	↓ Aβ(1–40/42) ↓ pGluAβ(3–40/42)	(92–94)
TBI Trauma	E64d (oral)	↓ motor deficits	↓ brain lesion	↓ CTSB, ↓ Bax	(45)
	CA-07Me (icv)	↓ memory deficits	↓ brain lesion	↓ CTSB, t-Bid, Bax, cyt.c, caspase 3	(47)
	z-DEVD-FMK (icv)	↓ motor & cognitive deficits	↓ brain lesion	↓ calpain, ↓ spectrin degradation	(102)
	LHVS (icv)	↓ grip strength	↓ brain edema	↓ IL-1β,↓ TNFα	(103)
Ischemia	E64c (ip, iv) E64d (ip) CA-074 (iv) CA-074Me (ip)	nd	↓ neuronal death, brain	↓ CTSB ↓ MAP2 degrad. ↓ caspase 3	(104–109)
Trauma cerebral bleeding	CP-1 (iv)	↓ motor deficits	↓ neuronal death, brain	↑ synaptophysin, brain	(110)
Excitatory Huntington’s disease	Z-FA-FMK (is)	nd	↓ brain lesion	nd	(111)
Excitatory epilepsy	CA-074Me (ip)	↑ learning ↑ neurolog. scores	nd	↓ CTSB ↓ LC3, ↓ beclin-1 ↓ bcl-2, ↓ PRG-1	(112)
Pain	CA-074Me (it)	↓ inflammatory pain	nd	↓ IL-1β, IL-18	(113)
Inflammatory pain, edema	K11777 (ip)	↓ inflammatory pain	↓ edema ↓ necrosis	↓ CTSB, CTSL, & CTSS ↓ c-fos	(114)
Meningitis infection	CA-074Me (ip)	nd	↑ clinical score	↓ IL-1β	(68)

Refs. indicate Reference citations

nd: not determined.

LTP, long-term potentiation; MS, multiple sclerosis; EAE, experimental atuoimmune encephalomyelitis; SCC, spinal cord contusion