RESUMO
Alzheimer's disease (AD) is the leading cause of dementia in the world, accounting for 50-75% of cases. Currently, there is limited treatment for AD. The current pharmacological therapy minimizes symptom progression but does not reverse brain damage. Studies focused on nonpharmacological treatment for AD have been developed to act on brain plasticity and minimize the neurotoxicity caused by the amyloid-beta (Aß) peptide. Using a neurotoxicity model induced by Aß in rats, the present study shows that physical (PE) and cognitive exercise (CE) reverse recognition memory deficits (with a prominent effect of long-term object recognition memory), decrease hippocampal lipid peroxidation, restore the acetylcholinesterase activity altered by Aß neurotoxicity, and seems to reverse, at least partially, hippocampal tissue disorganization.
RESUMO
Acetylcholinesterase (AChE; EC 3.1.1.7) plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-ß (Aß) peptide accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aß peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer's patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN 5706 for 10 weeks increases brain AChE activity in 7-month-old double transgenic mice (APP(SWE)-PS1) and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer's model. We concluded that early treatment with IDN 5706 decreases AChE-Aß interaction and this effect might be of therapeutic interest in the treatment of AD.