Introduction
Selenium
and seleno-compounds have been largely studied in diseases with
distinct aetiologies and development stages, such as cancer and
neurodegenerative diseases [1], [2], [3], [4], [5], [6].
With regards to the latter group, considerable research efforts are
ongoing, driven by the hope of obtaining therapeutics that are less
toxic and more effective than current treatments. Selenium has been
reported to exert diametral effects on the central nervous system (CNS),
showing both toxic and protective properties [7], [8].
Thus, several groups have focused on different strategies to
incorporate selenium into bioactive compounds and small molecules [9].
Over
the past 40 years, evidence in the scientific literature has
demonstrated that small selenium-containing compounds represent good
candidates in drug discovery, particularly because of their ability to
counteract cancer development and cellular oxidation [10].
The design, synthesis and testing of bioactive molecules has grown
exponentially, and the focus, at first limited to a few diseases, has
been rapidly extended to a larger spectrum of pathologies.
Here,
we provide a concise overview of the potential of selenium-containing
compounds, which represent a growing field of investigation for treating
neurodegenerative diseases. Specifically, we focus on two neurological
disorders that represent an open question for both scientists and
clinicians: Alzheimer’s disease (AD) and Parkinson’s disease (PD).
For
AD, there has been interest in dissecting the molecular mechanisms
involved in its onset to allow the development of new therapeutic
strategies [11].
The mechanisms responsible for the decline of cognitive abilities,
cytotoxicity, inflammation and the oxidative stress induced by amyloid-β
(Aβ) aggregates, all typical hallmarks of AD, have been extensively
dissected to identify specific molecular targets for the design of
highly selective small molecules. In this frame, some seleno-compounds,
alone or in combination with other molecules, have demonstrated efficacy
against stress oxidation and cytotoxicity, as well as against tau
tangles and Aβ aggregate accumulation (Figure 1) [12].
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FIGURE 1. The accumulation of Aβ plaques in the extracellular compartment and of tau protein tangles within neuronal cells in AD.
In the case of PD, selenium derivatives have been tested both in vitro and in vivo
for their ability to reduce neurotoxicity, cellular oxidation in the
brain and the typical symptoms of the disease. Hence, selenium
derivatives could represent a good strategy for new therapies [13].
Within
this keynote review, we critically discuss recent findings in the field
of selenium-based applications in neurological disorders, hand in hand
with their relative targets.
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