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Updated: Mar 26, 2026

Self-Assembly of Gamma-Modified Peptide Nucleic Acids into Complex Nanostructures in Organic Solvent Mixtures
Published on: June 26, 2020
D-SAL and NAP: Two Peptides Sharing a SIP Domain
Illana Gozes1, Shlomo Sragovich2, Yulie Schirer2
1The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Dr. Diana and Zelman Elton (Elbaum) Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and The Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, 69978, Israel. igozes@post.tau.ac.il.
Neuroprotective peptides NAP and D-SAL show promise in preventing diabetic neuropathy and improving cognitive function in rats. NAP demonstrated greater efficacy in later stages of neuropathy and cognitive enhancement.
Area of Science:
- Neuroscience
- Pharmacology
- Diabetology
Background:
- Diabetes mellitus causes significant neurological complications, including peripheral neuropathy and cognitive decline.
- Activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF) derivatives, NAPVSIPQ (NAP) and D-SALLRSIPA (D-SAL) respectively, exhibit neuroprotective properties.
- NAP is known to enhance microtubule stability, protect axonal transport, and inhibit apoptosis.
Purpose of the Study:
- To evaluate the therapeutic effects of NAP and D-SAL on behavioral deficits in a rat model of diabetes.
- To correlate behavioral outcomes with the known molecular mechanisms of NAP and D-SAL involving microtubule interactions.
Main Methods:
- A rat model of diabetes was utilized to assess peripheral neuropathy using thermal stimulus response.
- Cognitive function was evaluated through social and spatial memory tests (short-term, long-term, and reference memory).
- The role of the SIP (SxIP) motif in peptide-mediated neuroprotection was investigated mechanistically.
Main Results:
- Both NAP and D-SAL prevented immediate sensory neuropathy in diabetic rats.
- NAP treatment was effective in preventing a later neuropathic phase, while D-SAL was not.
- Both peptides improved cognitive performance, with NAP showing greater potency than D-SAL across various memory tasks.
Conclusions:
- NAP and D-SAL offer potential therapeutic strategies for managing diabetic neuropathy and associated cognitive impairments.
- The SIP (SxIP) motif is crucial for the neuroprotective effects of these peptides, likely through interaction with microtubule end-binding proteins.
- NAP demonstrates superior efficacy compared to D-SAL in mitigating advanced neuropathic symptoms and enhancing cognitive functions in diabetic rats.
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