The Neglected Role of Histamine in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques accumulation and cognitive impairment. Both environmental factors and heritable predisposition have a role in AD. Histamine is a biogenic monoamine that plays a role in several physiological functions, including induction of inflammatory reactions, wound healing, and regeneration. The Histamine mediates its functions via its 4 G-protein-coupled Histamine H1 receptor (H1R) to histamine H1 receptor (H4R). The histaminergic system has a role in the treatment of brain disorders by the development of histamine receptor agonists, antagonists. The H1R and H4R are responsible for allergic inflammation. But recent studies show that histamine antagonists against H3R and regulation of H2R can be more efficient in AD therapy. In this review, we focus on the role of histamine and its receptors in the treatment of AD, and we hope that histamine could be an effective therapeutic factor in the treatment of AD.

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

“…Reduced levels of histamine and urocanic acid, as well as increased 1-methylhistamine (Table 1) Alzheimer's disease (Naddafi and Mirshafiey, 2013). Thereby, AD has been previously associated with a loss of histaminergic neurons in the tuberomamillary nucleus (Nakamura et al, 1993) , 1998), in agreement with our findings in serum samples.…”

“…Reduced levels of histamine and urocanic acid, as well as increased 1-methylhistamine (Table 1) Alzheimer's disease (Naddafi and Mirshafiey, 2013). Thereby, AD has been previously associated with a loss of histaminergic neurons in the tuberomamillary nucleus (Nakamura et al, 1993), leading to a decline of histamine levels in different brain areas (Mazurkiewicz-Kwilecki and Nsonwah, 1989; Panula 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 et al, 1998), in agreement with our findings in serum samples.…”

Histaminergic modulation in Tourette syndrome

“…Overall, H3 receptors have also been implicated in suppressing histamine release in the brain. Therefore, pharmacological agents known to antagonize the H3 receptor and to regulate the H2 receptor have been proposed as promising treatment avenues for patients with Alzheimer disease [68]. Likewise, reduced histamine levels have also been demonstrated after bilateral carotid artery occlusion in rats, suggesting a potential role in vascular dementia [69].…”

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice

“…Importantly, we found that the inhibition of the H 3 R does not alter the motivational state of mice to drink nonalcohol tastants such as saccharin, which is a critical issue from a potential therapeutic development perspective. Our findings therefore suggest that antagonists of the H 3 R pathway, which are actively being developed for the treatment of several psychiatric disorders [24,[57][58][59][60], are potential pharmacological candidates that could be developed for the treatment of alcohol use and abuse disorders.…”