Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are two of the more common neurodegenerative diseases, with nearly seven million people in the US living with the conditions in 2023. While AD is more prevalent than ALS, they are both characterized by the progressive loss of specific neurons and glial cells in the central nervous system.
Research has demonstrated that the onset and progression of neurodegenerative diseases appear to be delayed or improved by the application of neurotrophic factors and that the derived peptide factors from these neurotrophic factors have been found to potentially restore neuronal function, improve behavioral deficits, and prolong their survival.
In this review, Ciesler and Sari review the role of trophic peptides in the improvement of AD and ALS with the goal of developing a better understanding of potential therapies for these neurodegenerative diseases.
While neurodegenerative diseases, including AD and ALS, are well documented to result in debilitating loss of memory and motor function, respectively, the specific mechanisms of action in these diseases are yet to be fully understood. However, research has found that the potential underlying mechanisms can be divided into two categories. The first, which is unique to each neurodegenerative disease, is a specific trigger that activates cell death machinery and the second, which appears to be universal among neurodegenerative diseases, is a directorial process to complete death of a neuron.
While there are currently no effective drugs for the treatment of neurodegenerative diseases, treatments of the symptoms associated with neurodegenerative diseases include neuroprotective factors, encompassing neurotrophins, and neuroprotective peptides. The authors focus this review on NAP peptide derived from activity neuroprotective protein and ADNF-9 peptide derived from activity-dependent neurotrophic factor (ADNF); both of these peptides have been shown to enhance cell survival and outgrowth of dendrites in the form of D-acid analogues.
NAP’s parent protein, ADNP, is essential for brain development and was found to protect neurons against severe oxidative stress. Studies examining NAP have found them to protect against neurotoxins while not affecting cell division. Considering these findings, NAP is now in phase II clinical trials with a primary focus on AD-related cognitive impairment. Additional studies are also evaluating the effects of NAP in ALS models associated with cytoskeletal dysfunction. NAP has been found to extend life span in ALS mouse models when administered prior to disease onset.
ADNF is released in response to vasoactive intestinal peptide that protects neurons from tetrodotoxin-induced cell death and is suggested to be essential for neuronal survival. ADNF-9 showed greater prevention of cell death associated with stress than other ADNF peptides; additional studies demonstrate that ADNF-9 suppressed SOD-1-mediated cell death. While prolonged survival of ALS mouse model was reported to be marginal, the authors highlight that the study did provide insight into a possible treatment for ALS.
The authors also highlight colivelin, a hybrid synthetic peptide of ANDF-9 and humanin, which was found to provide neuroprotection against AD-related memory loss and have a more potent neuroprotective effect than humanin and ADNF-9 when they are tested alone against neurotoxicity.
Ciesler and Sari conclude that in contrast to neurotrophic factors these trophic peptides have the ability to cross the blood-brain barrier for efficacy and have potential for future treatment of ALS and AD.
Source: “Neurotrophic Peptides: Potential Drugs for Treatment of Amyotrophic ….” 8 Apr. 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686488/.
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