Table 1.
Disease/Disorder Models used in the Studies Discussed in this Review
| Disease Model | Intervention | Cofilin Response | Outcome | Reference |
|---|---|---|---|---|
| AD (APPsw/PS1ΔE9) | PrPc knockout (APPsw/PS1ΔE9xPrnp−/−) | ? | Rescued axonal degeneration, synaptic markers, learning & memory deficits, & early death | Gimbel et al., 2010 |
| AD (APPsw/PS1ΔE9) | Reduce RanBP9 (APPsw/PS1ΔE9xRanBP9+/−) | ↓ | Reduced synaptic damage, gliosis, Aβ accumulation. Rescued LTP & memory | Woo et al., 2015b |
| AD (APPsw/PS1ΔE9) | Reduce Cofilin (APPsw/PS1ΔE9xCofilin+/−) | ↓ | Reduced synaptic protein loss, gliosis. Rescued LTP & contextual memory | Woo et al., 2015a |
| AD (APPsw/flo/lon/PS1M146L/L286V) | TAT-pS3 peptide injection | ↓ | Improved e-phys, working memory (T-maze) & novel object recognition | Deng et al., 2016 |
| AD (Aβ injection into ventricle, 5ng in 2.5 μl) | Scyllo-inositol co-injection with Aβ | ? | Reduce synaptic loss & activation of microglia | Jin and Selkoe, 2015 |
| AD (APPsw,du,iow/NOS2−/−) | Oral RAP-310 peptide | ? | Improved learning & memory in a radial arm water maze | Ruff, 2014 |
| Aggression (neonatal isolation) | Expression of cofilin S3A in the medial prefrontal cortex | ↑ | Normalized aggressive behavior and glutamatergic transmission | Tada et al., 2016 |
| Autism (Shank3+/ΔE21) | TAT-pS3 peptide injection | ↓ | Rescued social deficits, reduced repetitive behaviors, normalized NMDAR, synaptic actin localization & e-phys | Duffney et al., 2015 |
| Autism (Shank3+/ΔE21) | CA Rac1 virus injection | ↓ | Rescued social deficits & normalized NMDAR e-phys | Duffney et al., 2015 |
| Autism (NLG1−/−) | TAT-NLG-CTD injection or slice treatment | ↓ | Restored cofilin phosphorylation & LTP | Liu et al., 2016 |
| Brain inflammation (LPS injection) | DAPTA peptide injection | ? | Decreased neuroinflammatory response (activated microglia & astrocytes) | Rosi et al., 2005 |
| Manic/Bipolar (Sorbs2ΔE12) Sorbs2 encodes nArgBP2 | None performed | ? | Impaired memory & dendritic development | Zhang Q et al., 2016 |
| Manic/Bipolar (nArgBP2 siRNA) | Expression of Pak inhibitory domain or active cofilin S3A | ↑ | Rescued dendritic spine morphology in culture | Lee et al., 2016 |
| Neuropathic pain (nerve constriction) | Oral RAP-103 (DAPTA analog) | ? | Reduced pain-related behaviors, microglial activation & monocyte infiltration | Padi et al., 2012 |
| Neuropathic pain (nerve constriction) | ROCK inhibitor Y-27632 injection | ↑ | Reduced pain-related behaviors & decreased LIMK & cofilin phosphorylation | Qiu et al., 2016 |
| Neuropathic pain (nerve constriction) | TAT-S3 peptide injection | ↑ | Reduced pain-related behaviors | Qiu et al., 2016 |
| Neuropathic pain (nerve constriction) | Simvastatin (HMG CoA reductase inhibitor) | ↑ | Reduced pain-related behaviors, Rho membrane targeting, & LIMK & cofilin phosphorylation | Qiu et al., 2016 |
| Schizophrenic behavior (14-3-3 inhibitory peptide) | None Performed | N/A | Reduced levels of phospho- cofilin & spine density | Foote et al., 2015 |
| Schizophrenic behavior (14-3-3ζ knockout) | Clozapine | ? | Improved behavior but does not reverse spine defects | Cheah et al., 2012; Jaehne et al., 2015 |
| Sleep deprivation | Expression of cofilinS3D or knock-out of cAMP phosphodiesterase-4A5 | ↓ | Reduced spine loss & deficits in synaptic plasticity (e-phys) and improved long-term memory | Havekes et al., 2016 |
| Stroke (ischemia-reperfusion) | DAPTA peptide injection | ? | Improved neurological behavior, & reduced neuronal apoptosis & ROCK expression | Li et al., 2016 |
| Traumatic brain injury (rat) | AcSDKP peptide from Thymosin β4 | ? | Improved sensimotor function, spatial learning & spine number | Zhang Y et al., 2016 |