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Review Article

The endonuclease VIII-like proteins: new targets

in the treatment of ischemic stroke?

2
2
1,2
3
Long‑Xiu Yang , Wei Wang , Xiao Zhang , Qi Zhu , Qing Zhao , Gang Zhao 2
2
1 Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, China.
2 Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, Shaanxi, China.
3 Department of Microbiology, University of Oslo, N‑0424 Oslo, Norway.
ABSTRA CT
Oxidative deoxyribonucleic acid (DNA) damage is one of the major causes of neuronal injury in ischemia. The endonuclease
VIII‑like (NEIL) DNA glycosylases have a specific role in recognition and removal of oxidative DNA damage. The NEIL family
includes NEIL1, NEIL2, and NEIL3, that differ in substrate specificity, catalytic efficiency, and subcellular/tissue distribution.
This opens for a situation‑dependent phenotype in their absence. In this review, we will discuss the current knowledge on the
involvement of the NEILs in ischemic stroke and discuss the potential of these enzymes to serve as new targets in the treatment
of ischemic stroke.

Key words: Endonuclease VIII‑like proteins, ischemic stroke, targets

INTRODUCTION DNA damage can trigger cell death after the trauma,
[6]
especially in neurons which are more susceptible
According to the World Health Organization health to damage than astrocytes. Accumulated cell loss
[7]
report, stroke is the leading cause of disability in will gradually contribute to disease progression
adults and accounts for 5.5 million deaths worldwide, and eventually lead to poor prognosis in ischemic
equivalent to 9.6% of all deaths. Ischemic stroke is stroke. Maintaining genome integrity is essential
[1]
[8]
the most common type of stroke, accounting for about for cell survival and the main DNA repair system
87% of all stroke events. Oxidative stress, which for repairing oxidative DNA damage is base excision
[2]
is a disturbance in the oxidant‑antioxidant balance repair (BER). However, the exact impact of BER is
[9]
leading to the potential cellular damage, is widely still not fully understood, as most studies have been
recognized as one of the major factors contributing to performed in models where BER is either present
the pathophysiologic progressing of the brain in an or absent. As it is well known that unbalanced BER
ischemic stroke. Oxidative stress is also known to is detrimental to the cell, one might speculate that
[3]
play a role as a vital factor of ischemia reperfusion, suppressing full activation after ischemic insult could
which is one of the pathological events after ischemic be beneficial to restore cell. It should be remembered
brain. Oxidative stress not only could lead to that the killing period occurs after the stroke, during
[4]
structural changes of the proteins which can cause reperfusion when repair process is expected to be
the loss of biological activity, but also create oxidative maximal. The DNA repairing capacity of BER may
deoxyribonucleic acid (DNA) lesions in addition to affect the survival rate of neurons and change the
damage to other cellular constituents. Oxidative pathological outcome of ischemic stroke.
[5]
Corresponding Author: Prof. Gang Zhao, BER is initiated by DNA glycosylases that recognize
Department of Neurology, Xijing Hospital, The Fourth Military and excise the damaged bases of DNA. [10] Depending
Medical University, No. 169, Changle West Road,
Xi’an 710032, Shaanxi, China. on the type of lesion the BER pathway is initiated
E‑mail: zhaogang@fmmu.edu.cn
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Cite this article as: Yang LX, Wang W, Zhang X, Zhu Q, Zhao Q, Zhao G.
DOI: The endonuclease VIII-like proteins: new targets in the treatment of ischemic
10.4103/2347-8659.167308 stroke?. Neuroimmunol Neuroinflammation 2015;2:281-6.
Received: 24-04-2015; Accepted: 21-08-2015

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