Securinine Derivatives as Potential Anti-amyloid Therapeutic Approach.

Background: Oxidative stress and amyloid deposition are tightly interconnected pathological features of Alzheimer disease. In this respect, both amyloid production and aggregation may be stimulated by oxidative stress and also the increase of pathogenic β-amyloid and its aggregated form lead to oxidative stress progression. Therefore, the search for potential drugs with both antioxidant and antiaggregation properties are of great interest.

Neuroprotective Effects of the Securinine-Analogues: Identification of Allomargaritarine as a Lead Compound.

Oxidative stress and mitochondrial disturbances are the common and important causative factors of aging, and play an important role in the late onset of sporadic neurodegenerative diseases, including Alzheimer disease (AD). Furthermore, emerging evidence from in vitro and in vivo disease models suggests that oxidative stress and increased vulnerability to induction of mitochondrial permeability transition leads to the pathogenesis of the neurological disorders. Towards the goals of developing effective neuroprotectors, this article describes the synthesis and neuroprotective studies of various derivatives of the naturally occurring alkaloid securinine, based on which a lead compound, allomargaritarine (a diastereomer of margaritarine), was identified as an effective therapeutic for neuroprotection.

Biological Activities of QIAPI 1 as a Melanin Precursor and Its Therapeutic Effects in Wistar Rats Exposed to Arsenic Poisoning.

The chemical process initiated by QIAPI 1 has been deemed to be the most important biological reaction associated with human photosynthesis, and possibly neuroprotective effects under various inflammatory events. However, the detailed biological activities of QIAPI 1 as a melanin precursor are still unknown. In the present work, cytotoxicity test was done by MTT assay to determine cell viability of various cell lines (WI-38, A549, HS 683) like proliferation tests and its effect on cytokine production.

Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6 mice: Implications for modeling elderly depression.

The prevalence of depression increases with aging. We hypothesized that like humans, old animals exhibit anhedonic-like behavior, along with signs of behavioral despair. In rodents, anhedonia, a reduced sensitivity to reward, which is listed as a core feature of major depression in the DSM-IVR, can be measured by a decrease in intake of and preference for sweet solutions.

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice.

Pre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.