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by one of 11 different DNA glycosylases including The discovery of these three new DNA glycosylases
UNG1, UNG2, SUMUG1, thymine‑DNA glycosylase, generated strong interests by scientists to investigate
methyl‑binding domain 4, methylpurine‑DNA their biochemical functions and the corresponding
glycosylase, OGG1, muty glycosylase homologue, mechanisms. We summarize the substrate specificities
NTHL1, endonuclease VIII‑like (NEIL) 1, NEIL2, and of NEILs in Table 2.
NEIL3. [11] The subsequent pathway can divide into
two sub‑pathways: short‑patch BER (SP‑BER) and Interestingly, NEILs substrates largely overlap with
long‑patch BER (LP‑BER). [12] The repair processes the OGG1 and NTHL1 substrate spectra indicates that
consist of five steps: excision of the base, incision, NEILs may have a role in DNA repair that is unique to
end processing, and repair synthesis, including gap other DNA glycosylases.
filling and ligation. [11] In SP‑BER, a pol β‑mediated
single nucleotide incorporation is followed by strand NEIL1, NEIL2, and NEIL3 can also be distinguished
ligation, catalyzed by the XRCC1/DNA ligase III from each other by the preferred lesions in different
complex. If BER is initiated by NEILs glycosylases, DNA structures, which demonstrate their unique
after N‑glycosidic hydrolysis the termini is catalyzed biological roles in the regulation of cell cycle. NEIL1
by β,δ ‑elimination. Then the 3′‑phosphate is cleaved interacts with proliferating cell nuclear antigen (PCNA)
by polynucleotide kinase, producing a 1NT gap with and PCNA can stimulates NEIL1 activity suggesting
3′‑OH terminus. [13,14] LP‑BER is characterized by its special role in replication. [20] NEIL2 is involved
alternating flap endonuclease 1 cleavage and pols β in repairing oxidized bases in the transcribed genes
synthesis or the strand displacement DNA synthesis of mammalian cells, in particular, lesions in the
concerted by pols β and δ/ε. At last, the gap is sealed mutagenic cytosine oxidation product 5‑hydroxyuracil
by DNA ligase I. [14] OGG1, NTHL1, NEIL1, NEIL2, of the transcribed strand. In this function, NEIL2
and NEIL3 are recognized to be the five major DNA associates with ribonucleic acid (RNA) polymerase
glycosylases to remove oxidative base lesions. [10] NEILs II and the transcriptional regulator heterogeneous
play a critical role in the repair of oxidative DNA nuclear ribonucleoprotein‑U. [21] The NEIL3 repairs
damage. Accumulating evidence suggests that NEILs lesions in DNA with single‑stranded regions [22,23] and
may relate to diseases in central nervous system, this phenomenon may demonstrate its potential role
for example, ischemic stroke, neurodegeneration in cell proliferating, embryonic development, and
disease, and neurological autoimmune disease with neurogenesis.
consistent results. [15] However, our understanding of
the functions and potential uses of NEILs in ischemic NEIL1 expression patterns
stroke is still limited. Many studies have aimed at clarifying the expression
patterns of NEIL1. The NEIL1 shows ubiquitous
Thus, the purpose of this review is to summarize the expression in all tissues examined in a human, including
current knowledge on the involvement of the NEILs in the brain. [17‑19] More specifically, NEIL1 was identified in
ischemic stroke and aim to search for a new target in all brain regions analyzed in human, and especially in
the treatment of ischemic stroke. the cerebellum, neocortex, and hippocampus. Rolseth
[24]
et al. [24] showed that expression of NEIL1increases with
CHARACTERISTICS OF NEIL age by in situ hybridization studies in mouse brain.
Englander and Ma [25] found out that the expression
In 2002, several groups working independently of NEIL1 in the mature brain increases 1.5‑2.5‑fold
worldwide discovered three genes in the mouse compared to the embryonic brain.
and human genomes encoding DNA glycosylases
belonging to the Fpg/Nei superfamily and having a The NEIL1 activity has also been detected in
primary structure more similar to that of the NEIL mitochondria in the brain. [26] In accordance with
protein. [16‑19] These proteins were named NEIL1, NEIL2, its age‑dependent expression, the activity in
and NEIL3. [16‑19] The characteristics of human NEIL mitochondria also correlates with age, but with
genes and proteins are shown in Table 1. important differences: mitochondrial NEIL1 in the

Table 1: The characteristics of human NEIL genes and proteins
Gene Gene length Number Coding sequence, CL Amino Protein SL CCD C/I
nucleotides of exons nucleotides acids size (kDa)
NEIL1 8258 9 1173 15q24.2 390 43.6 N and M Yes I
NEIL2 17683 4 999 8p23.1 332 36.7 N and M Yes I
NEIL3 53102 10 1818 4q34.3 605 67.7 N Yes I
CL: chromosomal location; SL: subcellular location; N: nucleus; M: mitochondria; CCD: cell cycle dependent; C/I: constitutive or inducible protein

282 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 283