Aptamer and its applications in neurodegenerative diseases

Abstract

Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advancements of the technologies, aptamers have opened up new areas in this research field. Aptamers could bind with these related target proteins to interrupt their accumulation, subsequently blocking or preventing the process of neurodegenerative diseases. This review presents recent advances in the aptamer generation and its merits and limitations, with emphasis on its applications in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathy, Huntington's disease and multiple sclerosis.

Keywords: Alzheimer’s disease; Aptamer; Huntington’s disease; Multiple sclerosis; Neurodegenerative diseases; Parkinson’s disease; Transmissible spongiform encephalopathy.

Fig. 1

The processes of traditional SELEX, CE-SELEX, magnetic bead-based SELEX, and cell-SELEX. a The processes of traditional SELEX. It begins with the synthesis of a nucleic acid library. Then, the library is incubated with the target molecules for a period of time. The candidates with affinity can bind to the targets. Washing the unbound nucleic acids, the remaining binding molecules are amplified by PCR or RT-PCR. Then the molecules achieved from PCR or RT-PCR are used in the next cycle. b The processes of CE-SELEX. The nucleic acid library is incubated with the target molecules to form the mixtures. Then the mixtures are injected into the capillary. The bound nucleic acids are separated from unbound sequences through free solution capillary electrophoresis based on a mobility shift. c The processes of magnetic bead-based SELEX. The target molecules were immobilized on magnetic beads. Nucleic acid library is incubated with the target molecules on magnetic beads. Then the bound sequences are separated from unbound by magnetic force. d The processes of cell-SELEX. The nucleic acid library is incubated with negative cells which are not related to the target cells. Then, the unbound nucleic acids are collected and incubated with positive cells

Fig. 2

The damage of the aggregations of misfold proteins. Aβ and α-Syn are a class of proteins which are prone to aggregate and fold. The aggregations can disrupt the normal functions of cells and proteins, such as the impairment of the degradation systems, the dysfunction of mitochondria, the generation of oxidative stress, which could further lead to the disfunctions of cells, even apoptosis and death

Fig. 3

The aptamers (apt) against the AD targets. The hallmark of AD is Aβ of which the oligomer will disrupt the normal functions of cells. BACE1 can trigger the generation of Aβ, and B1-CT is a tail of BACE1. PrP^C is a receptor of Aβ oligomer. The aptamers against Aβ oligomers, B1-CT and PrP^C might be used as tools to diagnosis the Aβ oligomers and even prevent the generation of Aβ, which can decrease the serious effects to the cells

Fig. 4

The aptamers (apt) against the targets of PD. The pathology of PD is characterized by the presence of inclusions termed LBs whose major protein component is α-Syn, and the selective loss of dopaminergic neurons in the SN. α-Syn oligomers can also disrupt the normal functions of cells. So aptamers targeting α-Syn oligomers could be developed as useful tools for diagnosing PD or preventing the onset of PD. DA is another target, and aptamers against DA can diagnose the concentration of DA