12 Aptamers for the Diagnosis and Therapy …
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epitopes (Thr-231 and Ser-202) were isolated, and it is the first report to identify
tau epitope-specific aptamers. In addition, several of these aptamers could not only
inhibit tau phosphorylation, but also reduce monomeric p-tau and oligomeric p-tau
[66]. These aptamers can be used to detect tau in biofluids and uncover the mechanism
of tauopathy.
Therapeutic Strategies Targeting Tau
In order to inhibit tau aggregation, the aptamer directly binding to tau may also
prevent it aggregation. Kim et al. isolated an RNA aptamer (K d in the range of
40–200 nM), called Tau-1, against the longest isoform of human tau [67]. This
aptamer could efficiently prevent the oligomerization of tau both in vitro and in
HEK293 cells overexpressing the human tau protein, without affecting the degradation of tau. Moreover, the aptamer could significantly alleviate the neurotoxicity
caused by tau oligomer and the dendritic spine loss in primary hippocampal neurons,
which demonstrated that delaying tau assembly with RNA aptamers was an effective strategy for protecting cells under various neurodegenerative stresses originating
from pathogenic tau oligomerization.
In conclusion, the aptamers have been demonstrated as potential reagents for not
only monitoring the Aβ and tau aggregation, but also intervening the process of Aβ
and tau aggregation (Table 12.1), which suggests aptamers could be used as tools to
diagnose and therapy AD (Fig. 12.1).
12.2.2 The Applications of Aptamers in PD
PD is the second most common neurodegenerative disease mainly affecting 1%
of individuals above the age of 60. It is primarily defined by symptoms of motor
impairment, such as resting tremor, bradykinesia, postural instability, rigidity, and
so on [68–70]. One of the pathologic characteristics of PD is the presence of inclusions termed Lewy bodies (LBs) which are primarily composed of fibrillary α-syn
[71–73]. The aggregated α-syn exerts pathological effects such as the impairment
of synaptic vesicle, the dysfunction of mitochondria, the generation of inflammation, and oxidative stress, which in turn contributes to neurodegeneration. Another
pathologic characteristic of PD is the decrease of dopamine (DA) due to the death
of dopaminergic neurons in the substantianig ra pars compacta. Hence, aptamers
against α-syn and DA might contribute to the diagnosis or therapy of PD.
12.2.2.1 α-Syn
α-syn, the major protein component of LBs, is tending to misfold and aggregate
[72]. The aggregates of α-syn, especially the oligomers, have negative effects on the
neurons such as the impairment of the degradation systems, the damage of mitochondria, the generation of oxidative stress and endoplasmic reticulum stress, and so
357
epitopes (Thr-231 and Ser-202) were isolated, and it is the first report to identify
tau epitope-specific aptamers. In addition, several of these aptamers could not only
inhibit tau phosphorylation, but also reduce monomeric p-tau and oligomeric p-tau
[66]. These aptamers can be used to detect tau in biofluids and uncover the mechanism
of tauopathy.
Therapeutic Strategies Targeting Tau
In order to inhibit tau aggregation, the aptamer directly binding to tau may also
prevent it aggregation. Kim et al. isolated an RNA aptamer (K d in the range of
40–200 nM), called Tau-1, against the longest isoform of human tau [67]. This
aptamer could efficiently prevent the oligomerization of tau both in vitro and in
HEK293 cells overexpressing the human tau protein, without affecting the degradation of tau. Moreover, the aptamer could significantly alleviate the neurotoxicity
caused by tau oligomer and the dendritic spine loss in primary hippocampal neurons,
which demonstrated that delaying tau assembly with RNA aptamers was an effective strategy for protecting cells under various neurodegenerative stresses originating
from pathogenic tau oligomerization.
In conclusion, the aptamers have been demonstrated as potential reagents for not
only monitoring the Aβ and tau aggregation, but also intervening the process of Aβ
and tau aggregation (Table 12.1), which suggests aptamers could be used as tools to
diagnose and therapy AD (Fig. 12.1).
12.2.2 The Applications of Aptamers in PD
PD is the second most common neurodegenerative disease mainly affecting 1%
of individuals above the age of 60. It is primarily defined by symptoms of motor
impairment, such as resting tremor, bradykinesia, postural instability, rigidity, and
so on [68–70]. One of the pathologic characteristics of PD is the presence of inclusions termed Lewy bodies (LBs) which are primarily composed of fibrillary α-syn
[71–73]. The aggregated α-syn exerts pathological effects such as the impairment
of synaptic vesicle, the dysfunction of mitochondria, the generation of inflammation, and oxidative stress, which in turn contributes to neurodegeneration. Another
pathologic characteristic of PD is the decrease of dopamine (DA) due to the death
of dopaminergic neurons in the substantianig ra pars compacta. Hence, aptamers
against α-syn and DA might contribute to the diagnosis or therapy of PD.
12.2.2.1 α-Syn
α-syn, the major protein component of LBs, is tending to misfold and aggregate
[72]. The aggregates of α-syn, especially the oligomers, have negative effects on the
neurons such as the impairment of the degradation systems, the damage of mitochondria, the generation of oxidative stress and endoplasmic reticulum stress, and so