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Review
. 2017 Apr;12(4):534-537.
doi: 10.4103/1673-5374.205082.

Phosphatidylserine improves axonal transport by inhibition of HDAC and has potential in treatment of neurodegenerative diseases

Shiran Naftelberg  1 , Gil Ast  1 , Eran Perlson  2
Affiliations
Review

Phosphatidylserine improves axonal transport by inhibition of HDAC and has potential in treatment of neurodegenerative diseases

Shiran Naftelberg et al. Neural Regen Res. 2017 Apr.

Abstract

Familial dysautonomia (FD) is a rare children neurodegenerative disease caused due to a point mutation in the IKBKAP gene that results in decreased IKK complex-associated protein (IKAP) protein production. The disease affects mostly the dorsal root ganglion (DRG) and the sympathetic ganglion. Recently, we found that the molecular mechanisms underlying neurodegeneration in FD patients are defects in axonal transport of nerve growth factors and microtubule stability in the DRG. Neurons are highly polarized cells with very long axons. In order to survive and maintain proper function, neurons depend on transport of proteins and other cellular components from the neuronal body along the axons. We further demonstrated that IKAP is necessary for axon maintenance and showed that phosphatidylserine acts as an HDAC6 inhibitor to rescue neuronal function in FD cells. In this review, we will highlight our latest research findings.

Keywords: HDAC6; axonal transport; familial dysautonomia; microtubule; neurodegeneration; phosphatidylserine.

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Conflict of interest statement

Conflicts of interest: None declared.

Figures

Figure 1
Figure 1
A suggested model for the impaired axonal transport in familial dysautonomia (FD) and the effect of phosphatidylserine. A scheme representation of IKK complex-associated protein (IKAP) involvement in axonal transport in sensory neuron at (A) normal state, (B) Familial dysautonomia patients and (C) after phosphatidylserine treatment. (A) In normal state IKAP is part of a complex that acetylates α-tubulin and histone deacetylase 6 (HDAC6) is the major α-tubulin deacetylates. Acetylated α-tubulin is essential for dynein movement and polymerization of microtubules. (B) In FD, lower levels of IKAP are indicated and influence HDAC6 levels. As a result of the imbalance interplay in IKAP and HDAC6 levels, microtubule stabilization and axonal transport affected. (C) Phosphatidylserine elevates IKAP levels and downregulates HDAC6 levels and thus facilitates axonal transport and microtubule stabilization.
See this image and copyright information in PMC

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