Dimebon (
latrepirdine) is an anti-histaminergic agent which belongs to a fast-growing group of "old" medicines suggested to be of therapeutic utility for pathological conditions different from their original design ("repositioning"). Here, we overview the most recent studies on
Dimebon directed to
pathological processes in the brain-involving in vivo models of
proteinopathies. In the latter, neurodegenerative effects are attributed to a group of aggregate-prone
proteins such as γ-
synuclein, hyperphosphorylated tau, and fused in
sarcoma (FUS), which are engaged in numerous neurological diseases. We also focus on in vitro models comprised of cultured SH-SY5Y
neuroblastoma cells expressing mutant forms of transactive response
DNA binding protein 43 kDa (TDP-43) and showing a reduced number of TDP-43 inclusion-containing cells upon
Dimebon treatment along with activation of autophagy markers. Finally, we discuss
Dimebon's action in improving cellular energy balance, stabilizing mitochondrial function by increasing the threshold for nonselective mitochondrial pore opening, as well as increasing the
calcium retention capacity of mitochondria and reducing lipid peroxidation. Our results, together with data from other laboratories, warrant re-evaluation of the therapeutic potential of
Dimebon and its newly designed analogs as promising disease-modifying agents to treat
neurodegenerative disorders. Further, emerging data favor a possible anti-aging effect and application of
Dimebon for the treatment of depression, anxiety, and
ischemia. The most pronounced effect of
Dimebon is observed when treatment starts early in disease onset. This is a major factor which needs to be taken into account when planning future clinical trials.