Table 1.
Agents that interfere with mitogenic signaling pathways and molecules of the “expanded cell cycle”.
| Target | Agent | Stage/CNS Diseases |
|---|---|---|
| Tau solvent | TRx-0014 | Clinical use in AD (TauRx-Therapeutics-Ltd., 2007; Williams, 2009). |
| Antioxidants | Edaravone NXY-059 Coenzyme Q10 Vitamin E Melatonin Trolox SOD NAC PBN |
Clinical use in stroke in Asia (Wang and Shuaib, 2007; Abe, 2008) Clinical trials in stroke (Wang and Shuaib, 2007), AD (Berman and Brodaty, 2004; Vina et al., 2004; Park and Jin, 2008), ALS (Ferrante et al., 2005; Levy et al., 2006; Yoshino and Kimura, 2006). Experimental trials in ALS (Ito et al., 2008), PD (Yuan et al., 2008), SCI (Tanabe et al., 2009). |
| Glutamatergic modulators | Riluzole Ceftriaxone Talampanel MK-801 NBQX |
Clinical use in ALS (Andrews, 2009). Clinical trials in ALS (Andrews, 2009). Experimental trials in ICH (Ardizzone et al., 2004), stroke (Meden et al., 1993). |
| NMDA-receptor modulators | Memantine | Clinical use in AD (Danysz and Parsons, 2003; Molinuevo et al., 2005; Robinson and Keating, 2006; Iraqi and Hughes, 2009). Clinical trials in ALS (Andrews, 2009). Off-label use in psychiatric disorders (Zdanys and Tampi, 2008). |
| IL-1 inhibitors | Kineret Rytvela |
Experimental trials in hypoxic-ischemic newborn brain injury (Quiniou et al., 2008). |
| TNF-α inhibitors | Thalidomide CNI-1493 |
Experimental trials in AD (Li et al., 2004; Tweedie et al., 2007); PD (Li et al., 2004; Tweedie et al., 2007); stroke (Meistrell et al., 1997; Nawashiro et al., 1997; Barone and Parsons, 2000; Li et al., 2004; Tweedie et al., 2007). |
| Thrombin inhibitors | Hirudin | Experimental trials in ICH (Xue et al., 2006; Sun et al., 2008; Liu et al., 2009a). |
| Thrombin receptor-1 antagonist | BMS-200261 | Experimental trials in stroke (Junge et al., 2003); PD (Hamill et al., 2007). |
| Secretase inhibitors | OM 99-1 OM 99-2 BMS 289948 BMS 299897 |
Experimental trials in AD (Roberds et al., 2001; Ghosh et al., 2002; Selkoe, 2003; Anderson et al., 2005). |
| i/eNOS inhibitors | l-NAME AMT NPA |
Experimental trials in ICH (Lee da et al., 2006); SCI (Tanabe et al., 2009). |
| Cox-2 inhibitors | Rofecoxib Celecoxib NS-398 |
Clinical trials in AD (Etminan et al., 2003; Warner and Mitchell, 2004). Experimental trials in ICH (Lee da et al., 2006). |
| Ras inhibitors | Exoenzyme C3 Lovastatin |
Experimental trials in motor neuron disorders (Donovan et al., 1997; Smirnova et al., 2001). |
| Ca2+ channel blockers | Flunarizine | Clinical trials in stroke (Franke et al., 1996). |
| Calpain inhibitors | MDL-28170 | Experimental trials in AD (Jordan et al., 1997; Di Rosa et al., 2002; Battaglia et al., 2003). |
| Src Inhibitors | PP1 PP2 |
Experimental trials in ICH (Ardizzone et al., 2007; Liu et al., 2008; Liu et al., 2009a); AD (Williamson et al., 2002). |
| PI3K inhibitors | LY 294002 | Experimental trials in AD (Zhao et al., 2004). |
| JAK/Stat Inhibitors | EGCG | Experimental trials in AD, PD, HIV associated Dementia, multiple sclerosis (MS), ALS, or Pick's Disease (Tan, 2008). |
| GSK-3β inhibitors | Lithium Kenpaullone Indirubin SB 216763 SB 415286 |
Experimental trials in AD (Cross et al., 2001; Bhat et al., 2004; Jope and Johnson, 2004; Su et al., 2004; Dunn et al., 2005; Pallas and Camins, 2006). Clinical trials in ALS (Fornai et al., 2008; Andrews, 2009). |
| ERK1/2 kinase pathway | PD98059 | Experimental trials in ICH (Fujimoto et al., 2007; Ohnishi et al., 2007). |
| P38 kinase pathway | SB203580 SB239063 |
Experimental trials in ICH (Fujimoto et al., 2007); PD (Karunakaran et al., 2008); stroke (Barone et al., 2001). |
| JUN kinase pathway | CEP-1347 Colostrinin SP600125 |
Experimental trials in ICH (Fujimoto et al., 2007; Ohnishi et al., 2007); AD (Leszek et al., 2002; Wang et al., 2004); stroke (Kuan and Burke, 2005); PD (Wang et al., 2004; Kuan and Burke, 2005). |
| CDK inhibitors | Flavopiridol Olomoucine Roscovitine Quinazolines |
Experimental trials in AD (Copani et al., 2001; Jorda et al., 2003; Verdaguer et al., 2004b; Kruman, 2006; Mark Robert Barvian et al., 2006); PD (Kruman, 2006); stroke (Osuga et al., 2000; Wang et al., 2002); TBI (Di Giovanni et al., 2005; Hilton et al., 2008); SCI (Di Giovanni et al., 2003; Tian et al., 2006); excitotoxic stress(Park et al., 2000; Verdaguer et al., 2003b; Verdaguer et al., 2003a; Verdaguer et al., 2004a); optic nerve transection (Lefevre et al., 2002). |
| NF-κB pathway | KINK-1 | Experimental trials in stroke (Herrmann et al., 2005). |
4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine (PP1) 4-Amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide (PP2)
2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride (AMT)
2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX)
Epigallocatechin-3-gallate (EGCG)
Methythionium chloride (TRx-0014)
5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK 801)
N-acytyl-L-cysteine (NAC)
N(G)-nitro-l-arginine methyl ester (l-NAME)
N(omega)-propyl-l-arginine (NPA)
Phenyl-N-tert-butylnitrone (PBN)
Superoxide dismutase (SOD)