Epidemiological studies have associated tobacco consumption with a lower incidence of Alzheimer's disease (AD) and Parkinson's disease (PD). The neuroprotective effect of tobacco has been mainly attributed to the stimulation by nicotine of the α7 nicotinic acetylcholine receptors (nAChRs), which are implicated in neuronal survival, attention, and memory. A reduction in cholinergic function including lower levels of the expression of nAChRs in the hippocampus correlates with memory impairment in AD and schizophrenia. Although nicotine improves memory, sensory gating, and attention, its toxicity and undesired effects such as negative cardiovascular effects have terminated its therapeutic applications. Interestingly, its main metabolite cotinine shows similar neuroprotective and mnemonic properties but has a ten-fold longer half-life than nicotine and a good safety profile in humans. In neurodegenerative conditions including AD and PD, the accumulation of aggregated forms of the P-amyloid peptide correlates with cognitive impairment. Cotinine has been shown to reduce Ap aggregation in vitro. Additionally, since cotinine is a weak agonist of the nAChRs, we postulate that cotinine improves neuronal survival and memory at least in part by acting as a positive modulator of the α7 nAChRs. The potentiation of α7 nAChRs by cotinine can be beneficial in a broad range of neurological disorders such as schizophrenia, AD, attention-deficit hyperactivity disorder, and PD in which the modulation of these receptors can ameliorate working memory and attention. Based on actual evidence and these ideas, the relevance and potential therapeutic use of cotinine in several neurological disorders are discussed in this chapter. "Only do not forget, if I wake up crying it's only because in my dream I'm a lost child hunting through the leaves of the night for your hands...." - Pablo Neruda .
|Original language||English (US)|
|Title of host publication||Working Memory|
|Subtitle of host publication||Capacity, Developments and Improvement Techniques|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||23|
|State||Published - Feb 1 2011|
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