We study existing commercial drugs as potential neuroprotectants, to devise a multitask drug capable of inhibiting aggregation and neuroinflammation, while exhibiting good antioxidant activity in order to prevent mitochondrial damage.
These data highlight the urgent need to identify effective neuroprotective therapies to prevent the collapse of healthcare systems. In this scenario, treatments must directly target the pathogenesis of the underlying disease.
Since abnormal aggregation of specific proteins such as α-synuclein, tau, prion protein, or TDP-43, among others, seems to be the common cause of almost all neurodegenerative diseases, inhibiting these abnormal aggregations or promoting their degradation are the main objectives of drug design. Unfortunately, despite considerable investment in drug research and development, many attempts to date have failed.
Oxidative stress, mitochondrial dysfunction, and neuroinflammation have also been recognized as triggers for neuronal cell death in neurodegenerative disorders. There is compelling evidence showing that α-synuclein aggregation can trigger all these events, and sometimes vice versa, suggesting that these processes are intertwined and could foster a vicious cycle with fatal consequences for neurons.
Although a significant number of molecules are recognized as efficient in vitro inhibitors of α-synuclein amyloid self-assembly, they have failed to provide effective neuroprotection in vivo.
Furthermore, drugs developed to block these processes individually proved ineffective in clinical trials. Therefore, the big challenge right now is to focus on the search for molecules that target these multiple processes simultaneously in order to achieve an efficient neuroprotective effect. This means that we must devise a multitask drug capable of inhibiting aggregation and neuroinflammation, while exhibiting good antioxidant activity to prevent mitochondrial damage.