Available Technologies

Background

Alpha-synuclein (α-Syn) aggregates are associated with neurodegenerative diseases such as Parkinson's disease, Lewy body dementia, and multiple system atrophy. Although the N-terminal region of αSyn plays an important role in αSyn aggregation, most agents that detects αSyn target the C-terminal region, which is susceptible to degradation, making their practical use challenging. Furthermore, although some antibodies recognize the N-terminal region of αSyn, their large molecular size can hamper drug delivery. Thus, there have been no effective drugs against amyloid diseases.

Description and Advantages

RNA aptamers are a type of single-stranded oligonucleotides that bind strongly to specific molecules. A researcher at Kyoto University identified a novel RNA aptamer that binds to αSyn using 1-95 amino acids located in the N-terminal and the central region of αSyn.
The identified sequence of the aptamer binding located in the N-terminal region of αSyn (Fig. 1) and exhibited high inhibitory effects on αSyn aggregation (Fig. 2).

➢ Strong binding to the N-terminal region of αSyn

　The C-terminal region of αSyn degraded during the aggregation process, but the N-terminal region remains unprocessed in amyloid fibrils.

➢ Inhibition of amyloid protein aggregation

　The novel aptamer is capable of binding to tau in addition to αSyn thus can be potentially used as a prophylactic or therapeutic agent diverse amyloid diseases.

➢ Aptamer sequence of 21 nucleotides in length

　Combined with other methods, delivery to the brain is also possible.

➢ Inexpensive and synthesizable

Drugs for specifically recognizing the N-terminal have not been available to date.
(The N-terminal region plays an important role for aggregation.)

Fig. 1 Overview of the Invention

The binding region (1-95) to the aptamer of this invention is highlighted in green.

Fig. 2 Inhibition of αSyn aggregation by the novel RNA aptamer (HEK293 cells)

An αSyn seeding assay was performed using the FRET method. The novel RNA aptamer inhibited the αSyn aggregation, resulting in no FRET (excitation of YFP) signals and decreased aggregation seeds (puncta) shown in green.