Putative neuroprotective agents in neuropsychiatric disorders

Abstract

In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders.

Obesity and psychiatric disorders: Commonalities in dysregulated biological pathways and their implications for treatment

“…Potentially, suffering from both conditions may increase neuroprogressive pathways and lead to worsening treatment outcomes, relapse or treatment resistance. Adjunct interventions that may be considered include the addition of anti-inflammatory drugs such as COX-2 inhibitors (Muller and Schwarz, 2008) and the TNF antagonist, infliximab (Raison et al, 2013), medications with neuroprotective properties (e.g., antidepressants, mood stabilisers) (Dodd et al, 2013, Malhi et al, 2012, herbs and nutrients with anti-inflammatory and antioxidant properties (e.g., curcumin, resveratrol, omega-3 fatty acids, green tea, n-acetyl cysteine, CoQ10, selenium, zinc, alpha lipoic acid and vitamins such as A, C and E) (Alappat and Awad, 2010, Floyd, 1999, Kim et al, 2008, Lopresti et al, 2012, Scapagnini et al, 2012 and lifestyle changes known to enhance neurogenesis (e.g., sleep hygiene interventions, meditation, yoga, relaxation therapies and exercise) (Doraiswamy and Xiong, 2007, Kiecolt-Glaser et al, 2010, Lopresti et al, 2013.…”

The emerging pharmacology and function of GPR35 in the nervous system

“…Recent literature has suggested that some of the benefits 477 exerted by aspirin could be mediated by GPR35 (Dodd et al, 2013). This is based in part on studies 478 designed to understand how aspirin application inhibits acute inflammation, irrespective of its effects 479 on the inhibition of prostaglandin synthesis.…”

Design, Synthesis, and Potent Antiepileptic Activity with Latent Nerve Rehabilitation of Novel γ-Aminobutyric Acid Derivatives

“…Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. 8) A recent study 9) has demonstrated that chronic treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, resulted in a remarkable decrease in the frequency of spontaneous recurrent seizures (SRS) after pilocarpine-induced prolonged seizures.…”