Background:
Neuronal Microtubule (MT) tau protein, providing cytoskeleton to neuronal
cells, plays a vital role, including maintenance of cell shape, intracellular transport, and cell division.
Tau hyperphosphorylation mediated MT destabilization results in axonopathy, additionally neurotransmitter
deficit and ultimately causing Alzheimer's disease. Pre-clinically, streptozotocin (3mg/kg, 10μl/
unilateral, ICV) stereotaxically mimics the behavioral and neurochemical alterations similar to Alzheimer's
tau pathology resulting in MT assembly defects further lead to neuropathological cascades.
Objective:
Clinically approved medications such as Donepezil (DNP), rivastigmine, and Memantine
(MEM) are responsible for symptomatic care only, but there is no specific pharmacological intervention
that directly interacts with the neuronal microtubule destabilization.
Methods:
The current study focused on the involvement of anti-cancer agent microtubule stabilizer cabazitaxel
at a low dose (0.5 and 2 mg/kg) alone and in combination with standard drugs DNP (5 mg/kg),
MEM (10 mg/kg) and microtubule stabilizer Epothilone D (EpoD) (3 mg/kg) in the prevention of intracerebroventricular
streptozotocin (ICV-STZ) intoxicated microtubule-associated tau protein hyperphosphorylation.
Results:
Chronic treatment of CBZ at a low dose alone and in combination with standard drugs showing
no side effect and significantly improve the cognitive impairment, neurochemical alterations along with
reducing the level of hyperphosphorylated tau by preventing the breakdown of the neuronal cytoskeleton,
respectively.
Conclusion:
The above findings suggested that CBZ at low dose show neuroprotective effects against
ICV-STZ induced microtubule-associated tau protein hyperphosphorylation in rats and may be an effective
agent for the preventive treatment of AD.
O1-06-08: Caspase-6 activation disrupts the human neuronal cytoskeleton: Strong implication for an early cause of neuronal disruption in mild cognitively impaired and Alzheimer's disease individuals
