440
H. Jin
human serum and cerebrospinal fluid samples. Aβ42 and tau441 can be simultaneously recognized and detected using two magnetic probes with different morphologies. The results were in close agreement with those obtained through ELISA, this
advanced and intelligently engineered assay has great potential as a practical tool for
the prognosis and diagnosis of AD.
The main pathological markers of Alzheimer’s disease (AD) is Amyloid-β (Aβ)
plaque situated in the brain β-site amyloid precursor protein-cleaving enzyme
(BACE1) and γ-secretase can degrade APP to induce the production of Aβ. Thus,
inhibition of BACE1 may be a target therapy scheme for AD. Xingmei Zhang group
selected a DNA aptamer based on the human BACE1 extracellular domain, named
A1. The A1 aptamer specifically bound to BACE1 and decreased Aβ40 and Aβ42
production as well as sAPPβ expression in the AD cell model (M17-APPsw cells).
Further, The A1 aptamer was intracerebroventricularly injected to Tg 6799 mice (an
effective AD animal model), subsequent behavioral experiments showed that treatment with the aptamer A1 improved the cognitive abilities of the AD mice [230].
This preclinical study indicates aptamer A1 is a promising potential tool for AD
treatment.
Parkinson’s disease (PD) [231], the most common age-related motoric neurodegenerative disease and only second to AD in occurrence frequency, manifested as a
characteristic movement disorder and was associated with cognitive impairment and
progressive disability. It was initially described in the 1800 s by James Parkinson as
the “Shaking Palsy”. PD affects about 5 million people worldwide with no disease
modifying therapies.
Loss or decrease of secretion of the neurotransmitter dopamine was recognized as the pathophysiology of the motor dysfunction. Thus, dopamine is a sensitive biomarker or therapeutic target for monitoring and treatment of PD. In 1997,
Mannironi et al. [232] selected the first RNA dopamine aptamer, named dopa2. This
aptamer was truncated from 96nt to 57nt, named dopa1.30/c.30, with a Kd of 0.7 μM.
Álvarez-Martos further constructed RNA aptamer/cysteamine-modified electrodes
to detect dopamine in undiluted human serum samples [233].
McConnell et al. [234] develop a system to transport two dopamine aptamers
through the blood-brain barrier (Fig. 14.5). This system uses a liposome vehicle
that is surface-modified with two different dopamine-binding aptamers that bind
to the transferrin receptor. The multi-aptamer payload/targeting system successfully transfers aptamer into the brain, and systemic pretreatment with the dopamine
aptamer-loaded liposomes reduces cocaine-induced hyperlocomotion. This work is
the first example of an IP delivered multi-aptamer payload/targeting system to cross
the blood-brain barrier and successfully attenuate behavior in an animal model of
mental illness-associated behaviors. It also paves the way for PD’s target therapy in
the future.
Except for dopamine, alpha-synuclein (α-syn) [235] is another major constituent
of Lewy bodies that are the most important toxic species in the brains of PD patients.
Mutations of the α-syn coding gene lead to familial PD [236], α-syn is a promising
candidate as a biomarker for PD diagnosis based on the alteration in blood, plasma,
or cerebrospinal fluid.
H. Jin
human serum and cerebrospinal fluid samples. Aβ42 and tau441 can be simultaneously recognized and detected using two magnetic probes with different morphologies. The results were in close agreement with those obtained through ELISA, this
advanced and intelligently engineered assay has great potential as a practical tool for
the prognosis and diagnosis of AD.
The main pathological markers of Alzheimer’s disease (AD) is Amyloid-β (Aβ)
plaque situated in the brain β-site amyloid precursor protein-cleaving enzyme
(BACE1) and γ-secretase can degrade APP to induce the production of Aβ. Thus,
inhibition of BACE1 may be a target therapy scheme for AD. Xingmei Zhang group
selected a DNA aptamer based on the human BACE1 extracellular domain, named
A1. The A1 aptamer specifically bound to BACE1 and decreased Aβ40 and Aβ42
production as well as sAPPβ expression in the AD cell model (M17-APPsw cells).
Further, The A1 aptamer was intracerebroventricularly injected to Tg 6799 mice (an
effective AD animal model), subsequent behavioral experiments showed that treatment with the aptamer A1 improved the cognitive abilities of the AD mice [230].
This preclinical study indicates aptamer A1 is a promising potential tool for AD
treatment.
Parkinson’s disease (PD) [231], the most common age-related motoric neurodegenerative disease and only second to AD in occurrence frequency, manifested as a
characteristic movement disorder and was associated with cognitive impairment and
progressive disability. It was initially described in the 1800 s by James Parkinson as
the “Shaking Palsy”. PD affects about 5 million people worldwide with no disease
modifying therapies.
Loss or decrease of secretion of the neurotransmitter dopamine was recognized as the pathophysiology of the motor dysfunction. Thus, dopamine is a sensitive biomarker or therapeutic target for monitoring and treatment of PD. In 1997,
Mannironi et al. [232] selected the first RNA dopamine aptamer, named dopa2. This
aptamer was truncated from 96nt to 57nt, named dopa1.30/c.30, with a Kd of 0.7 μM.
Álvarez-Martos further constructed RNA aptamer/cysteamine-modified electrodes
to detect dopamine in undiluted human serum samples [233].
McConnell et al. [234] develop a system to transport two dopamine aptamers
through the blood-brain barrier (Fig. 14.5). This system uses a liposome vehicle
that is surface-modified with two different dopamine-binding aptamers that bind
to the transferrin receptor. The multi-aptamer payload/targeting system successfully transfers aptamer into the brain, and systemic pretreatment with the dopamine
aptamer-loaded liposomes reduces cocaine-induced hyperlocomotion. This work is
the first example of an IP delivered multi-aptamer payload/targeting system to cross
the blood-brain barrier and successfully attenuate behavior in an animal model of
mental illness-associated behaviors. It also paves the way for PD’s target therapy in
the future.
Except for dopamine, alpha-synuclein (α-syn) [235] is another major constituent
of Lewy bodies that are the most important toxic species in the brains of PD patients.
Mutations of the α-syn coding gene lead to familial PD [236], α-syn is a promising
candidate as a biomarker for PD diagnosis based on the alteration in blood, plasma,
or cerebrospinal fluid.