Shozawa_2018_Neurosci.Lett_677_19

Reference

Title : Supratherapeutic concentrations of cilostazol inhibits beta-amyloid oligomerization in vitro - Shozawa_2018_Neurosci.Lett_677_19
Author(s) : Shozawa H , Oguchi T , Tsuji M , Yano S , Kiuchi Y , Ono K
Ref : Neuroscience Letters , 677 :19 , 2018
Abstract :

Alzheimer disease (AD) is the most common type of dementia, and is currently incurable. The efficacy of existing treatments for AD such as acetylcholinesterase inhibitors is limited to symptom improvement. Research on disease-modifying therapies (DMTs) has conventionally focused on amelioration of CNS pathogenesis. Two neuropathological changes correlate strongly with AD, the appearance of neurofibrillary tangles containing the microtubule-associated protein tau and extracellular amyloid deposits containing amyloid beta-protein (Abeta). The aggregation of Abeta is believed to be the key pathogenic event in AD, with oligomeric assemblies thought to be the most neurotoxic form. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for AD patients. The clinical phosphodiesterase type-3 inhibitor cilostazol (CSZ) was recently found to suppress the progression of cognitive decline in patients with stable AD receiving acetylcholinesterase inhibitors. Here we examined the effects of CSZ on in vitro aggregations of Abeta1-40 and Abeta1-42 including oligomerization, using the thioflavin T assay, photo-induced cross-linking of unmodified proteins, and electron microscopy. CSZ (25-100muM) inhibited Abeta aggregation, especially oligomer formation. Considering that CSZ might be a key molecule for DMTs of AD, it cannot be ruled out that the low concentration of CSZ achievable in patient dosing may display some ant-oligomeric activity in synergy with its known therapeutic effects.

PubMedSearch : Shozawa_2018_Neurosci.Lett_677_19
PubMedID: 29684530

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Citations formats

Shozawa H, Oguchi T, Tsuji M, Yano S, Kiuchi Y, Ono K (2018)
Supratherapeutic concentrations of cilostazol inhibits beta-amyloid oligomerization in vitro
Neuroscience Letters 677 :19

Shozawa H, Oguchi T, Tsuji M, Yano S, Kiuchi Y, Ono K (2018)
Neuroscience Letters 677 :19