Title:Understanding the Role of Histone Deacetylase and their Inhibitors in
Neurodegenerative Disorders: Current Targets and Future Perspective
Volume: 20
Issue: 1
Author(s): Vishal Kumar, Satyabrata Kundu, Arti Singh and Shamsher Singh*
Affiliation:
- Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab,India
Keywords:
HDACs, SIRTs, neurodegenerative disorder, neuroprotection and neurotoxic effect, future targets
Abstract: Neurodegenerative diseases are a group of pathological conditions that cause motor incordination
(jerking movements), cognitive and memory impairments result from degeneration of
neurons in a specific area of the brain. Oxidative stress, mitochondrial dysfunction, excitotoxicity,
neuroinflammation, neurochemical imbalance and histone deacetylase enzymes (HDAC) are known
to play a crucial role in neurodegeneration. HDAC is classified into four categories (class I, II, III
and class IV) depending upon their location and functions. HDAC1 and 2 are involved in neurodegeneration,
while HDAC3-11 and class III HDACs are beneficial as neuroprotective. HDACs are
localized in different parts of the brain- HDAC1 (hippocampus and cortex), HDAC2 (nucleus),
HDAC3, 4, 5, 7 and 9 (nucleus and cytoplasm), HDAC6 & HDAC7 (cytoplasm) and HDAC11 (Nucleus,
cornus ammonis 1 and spinal cord). In pathological conditions, HDAC up-regulates glutamate,
phosphorylation of tau, and glial fibrillary acidic proteins while down-regulating BDNF, Heat
shock protein 70 and Gelsolin. Class III HDACs are divided into seven sub-classes (SIRT1-SIRT7).
Sirtuins are localized in the different parts of the brain and neuron -Sirt1 (nucleus), Sirt2 (cortex,
striatum, hippocampus and spinal cord), Sirt3 (mitochondria and cytoplasm), Sirt4, Sirt5 & Sirt6
(mitochondria), Sirt7 (nucleus) and Sirt8 (nucleolus). SIRTs (1, 3, 4, and 6) are involved in neuronal
survival, proliferation and modulating stress response, and SIRT2 is associated with Parkinsonism,
Huntington’s disease and Alzheimer’s disease, whereas SIRT6 is only associated with Alzheimer’s
disease. In this critical review, we have discussed the mechanisms and therapeutic targets of
HDACs that would be beneficial for the management of neurodegenerative disorders
