Table 1.

Present main therapies for CNS diseases with documented information involving NOX enzymes

Disease	Drugs	Pharmacodynamic	Effect	Therapeutic benefit	Main issues	Comments	Ref.
Alzheimer	Tacrine, donepezil, rivastigmine, galantamine	Acetylcholinesterase inhibitors	Increase the level of acetylcholine	Improvements of cognitive functions	Benefic effects are often modest and only temporary	These drugs do not decrease disease progression	[24, 103]
	Memantine	Non-competitive NMDA receptor antagonist	Protects from glutamate excitotoxicity
ALS	Riluzole	Not defined	Protects from glutamate excitotoxicity	Increase survival by 3 months	Absence of subjective benefits while drug is expensive	Unique therapeutic option, well tolerated	[105]
Parkinson	Levodopa (L-DOPA) Sinemet or Madopar	Precursor of dopamine	Increase dopamine levels	Improvement of motor symptoms	Dyskinesia, dystonia, motor fluctuation	Drugs often used in combination	[26, 121]
	Apomorphine, bromocriptine, cabergoline, dihydroergocryptine, lisuride, pergolide, piribedil, pramipexole,ropinirole and rotigotine.	Dopamine agonists	Binds to postsynaptic dopamine receptor: mimicks the effect of dopamine		Lower efficacy than L-dopa, but less side effects
	Selegiline rasaligine	Monoamine oxidase inhibitors	Increase level of dopamine
Schizophrenia	Antipsychotics	Mainly D2 receptor antagonists	Decrease dopamine action	Reduce positive symptoms	Severe side effects (sedation, extra-pyramidal motor disabilities) low compliance, drug resistance	No improvement of social functionality no effect on negative symptoms	[71]
Ischemic stroke	IV or IA tissue plasminogen activator (t-PA) within 3 – 4.5 h of symptom onset	Thrombolysis	Decrease vessel occlusion	Recanalization	Risk of intracerebral hemorrhage	Treatment is limited to early phases after stroke, and does not reduce the brain damage	[99]
	MERCI device	Mechanical thrombectomy			Still under clinical investigation
Obstructive sleep apnea	Application of devices to induce a continuous positive airway pressure	Delivering compressed air to avoid obstruction of the upper airway		Reduce or prevent apnea	Non-compliance Patients consider the device uncomfortable		[51]
Multiple sclerosis	Interferon (IFN)-β	Recombinant interferon β	Prevent inflammation	Reduction in the rate of MS relapses, and to slow the progression of disability in MS	Lymphopenia, severe depression and injection site necrosis	Real efficacy is controversial	[14, 40, 162]
	Glatiramer acetate	Random polymer of four amino acids of myelin basic protein	Immunomodulator: decoy diverting an autoimmune response against myelin	Decreases frequency of relapses and slow progression of disease	Reaction at injection site	Long term improvement and similar efficiency as interferon Beta	[25]
	Natalizumab	Humanised monoclonal antibody to α4-integrin	Decrease penetration of T lymphocytes in the CNS	Reduces progression and decreases relapsing rate	Development of progressive multifocal leukoencephalopathy	Use limited to severe relapsing remitting MS and not responding to interferonBeta	[6, 64]
	Mitoxantrone	Type II topoisomerase inhibitor	Immunosuppressant	Especially used in secondary progressive MS	Cardiotoxicity and risk of leukemia	Non specific; antineoplastic agent	[98, 100]
	Fingolimod	Binding of sphingosine 1-phosphate receptor	Immunosuppressant: Inhibit T lymphocytes excavation from lymphoid tissue	Decreases relapsing rate	Increased infection risk	Novel pharmacological approach; Recently approved by the FDA (2010)	[48, 125]
Guillain Barré	Plasma exchange and Intravenous immuno globulin	N/A	Diversion of autoimmune response	reduction of stays in intensive care unit and long-term disability	Randomised trials have low statistical power due to low number of patients	Emergency action, not a treatment	[59, 93]