Diterpenes and the crosstalk with the arachidonic acid pathways, relevance in neurodegeneration

Juan M. Zolezzi; Nibaldo C. Inestrosa

doi:10.4103/1673-5374.257521

摘要：Dementia has emerged as one of the main threats to human health in the modern civilization. Increased aging of world population and unhealthy lifestyle habits have been identified as critical factors able to facilitate dementia establishment. In this context, according to the Alzheimer’s Research International, Alzheimer’s disease (AD) constitutes the primary cause of de-mentia worldwide and its numbers are expected to grow during the following years. Clinically, AD is characterized by the pro-gressive decline in the cognitive performance as well as by an altered social behavior. Initially affecting the short-term mem-ory, the long-term memory becomes compromised as the pa-thology progresses. Relevantly, the severe cognitive impairment observed in AD reflects the dramatic effects of the pathology to the hippocampus and to the brain cortex circuitry, character-ized by synaptic damage and neuronal loss. Histopathologically, AD displays two pathognomonic lesions within the brain pa-renchyma: the extraneuronal senile plaques, which are consti-tuted by aggregated forms of the amyloid-β (Aβ) peptide, and the intraneuronal formation of neurofibrillary tangles (NFTs), constituted mainly of hyperphosphorylated tau protein. As re-ported elsewhere, it is important to note that additional features develop during AD, playing a critical role in its pathophysiol-ogy. Severe neuroinflammation, represented by glial reactivity and increased levels of pro-inflammatory mediators, vascular disease, mitochondrial dysfunction, calcium dyshomeostasis, and oxidative stress, are some of the most relevant alterations observed during AD. Regrettably, despite significant resources committed to the study of AD, no effective therapy is currently available to improve patient’s outcome. Thus, the evaluation of potentially useful molecules able to modulate the progression of the disease remains an urgent need to be satisfied in the context of AD research.