12 Aptamers for the Diagnosis and Therapy …
361
DA may be another tool to monitor DA concentration and explore the pathological
mechanism of PD (Fig. 12.2).
Diagnostic Strategies Targeting DA
The first RNA aptamer against DA called dopa2, selected by Mannironi et al. in
1997, could bind to DA with high affinity (with a K d of 1–3 μM) and specificity [86].
Then a particular type of aptamer, called “ribonucleopeptide” (RNP), was selected
against DA with K d of 3–15 mM [87]. Interestingly, these aptamers could be easily
converted into fluorescent sensors by modification of the N-terminal of the peptide
with different fluorophores. Two of these aptamers, named DH05 and DHc65 (K d
in the range of 1–1.5 μM), were used to construct ratiometric fluorescent sensors to
detect DA in vitro [88].
Then the aptamer was used to build as label-free electrochemical aptasensor for
detecting DA by Liu et al. in 2012. The aptasensor had been successfully tested the
DA in human serum with high sensitivity and selectivity [89]. However, DA analysis
is complicated by the interference from other electrochemically active endogenous
compounds present in the brain, including dopamine precursors and their metabolites and other neurotransmitters. So another RNA aptamer-based electrochemical
biosensor for selective and label-free analysis of DA in the presence of other neurotransmitters was reported by Farjami et al. in 2013 [90]. To further enhance the
detecting accuracy, Li et al. developed a new nanoelectronic device (by modifying
aptamers on a multiple-parallel-connected silicon nanowire field-effect transistor) as
a biosensor for detecting DA. This biosensor can be able to detect DA at the extremely
low concentration level (<10
−10 M) in the extracellular fluid of PD patients and in
the urine/blood of patients. This biosensor was also applied to monitor the released
DA under hypoxic stimulation from PC12 cells [91]. These studies demonstrated
that aptamers against DA might be used as tools to diagnose PD.
In sum, the aptamers, have been indicated as potential tools for not only monitoring
α-syn aggregation and DA, but also intervening the process of α-syn aggregation
(Table 12.2), which suggests aptamers could be used as reagents to diagnose and
treat PD (Fig. 12.2).
12.2.3 The Applications of Aptamers in TSEs
TSEs is one class of neurodegenerative disorders, affecting human beings
(Creutzfeldt–Jakob disease) and other mammals (bovine spongiform
encephalopathy) [92]. The pathological characteristic of TSEs is the conversion of normal cellular prion protein (PrP
C ), α-helix-rich isoform, to abnormal PrP
Sc
subtypes, β-sheet-rich isoform, and PrP
Sc protein accumulation in the brain [93].
Thus, discriminating between PrP
C and PrP
Sc , as well as inhibiting the transformation from PrP
C into PrP
Sc , might be useful approaches to study the pathogenesis of
TSEs, further diagnose and treat them.
361
DA may be another tool to monitor DA concentration and explore the pathological
mechanism of PD (Fig. 12.2).
Diagnostic Strategies Targeting DA
The first RNA aptamer against DA called dopa2, selected by Mannironi et al. in
1997, could bind to DA with high affinity (with a K d of 1–3 μM) and specificity [86].
Then a particular type of aptamer, called “ribonucleopeptide” (RNP), was selected
against DA with K d of 3–15 mM [87]. Interestingly, these aptamers could be easily
converted into fluorescent sensors by modification of the N-terminal of the peptide
with different fluorophores. Two of these aptamers, named DH05 and DHc65 (K d
in the range of 1–1.5 μM), were used to construct ratiometric fluorescent sensors to
detect DA in vitro [88].
Then the aptamer was used to build as label-free electrochemical aptasensor for
detecting DA by Liu et al. in 2012. The aptasensor had been successfully tested the
DA in human serum with high sensitivity and selectivity [89]. However, DA analysis
is complicated by the interference from other electrochemically active endogenous
compounds present in the brain, including dopamine precursors and their metabolites and other neurotransmitters. So another RNA aptamer-based electrochemical
biosensor for selective and label-free analysis of DA in the presence of other neurotransmitters was reported by Farjami et al. in 2013 [90]. To further enhance the
detecting accuracy, Li et al. developed a new nanoelectronic device (by modifying
aptamers on a multiple-parallel-connected silicon nanowire field-effect transistor) as
a biosensor for detecting DA. This biosensor can be able to detect DA at the extremely
low concentration level (<10
−10 M) in the extracellular fluid of PD patients and in
the urine/blood of patients. This biosensor was also applied to monitor the released
DA under hypoxic stimulation from PC12 cells [91]. These studies demonstrated
that aptamers against DA might be used as tools to diagnose PD.
In sum, the aptamers, have been indicated as potential tools for not only monitoring
α-syn aggregation and DA, but also intervening the process of α-syn aggregation
(Table 12.2), which suggests aptamers could be used as reagents to diagnose and
treat PD (Fig. 12.2).
12.2.3 The Applications of Aptamers in TSEs
TSEs is one class of neurodegenerative disorders, affecting human beings
(Creutzfeldt–Jakob disease) and other mammals (bovine spongiform
encephalopathy) [92]. The pathological characteristic of TSEs is the conversion of normal cellular prion protein (PrP
C ), α-helix-rich isoform, to abnormal PrP
Sc
subtypes, β-sheet-rich isoform, and PrP
Sc protein accumulation in the brain [93].
Thus, discriminating between PrP
C and PrP
Sc , as well as inhibiting the transformation from PrP
C into PrP
Sc , might be useful approaches to study the pathogenesis of
TSEs, further diagnose and treat them.