










































  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

 
 

 
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. 

INVESTIGATING  
MIMETICS OF A PEPTIDE 

DERIVED FROM THE  
EFFECTOR DOMAIN OF 

MARCKS 
AS POSSIBLE  

THERAPEUTICS FOR  
SPINAL CORD INJURY 

MONICA TSCHANG, 
MELITTA SCHACHNER (FACULTY ADVISOR) 

 

 

 

✵ ABSTRACT 
Like other conditions affecting the central 

nervous system, spinal cord injury (SCI) is difficult to 
treat with molecular therapies because the blood-
brain barrier makes intravenous treatments largely 
ineffective. For example, a synthetic peptide chain 
derived from the effector domain (ED) of myristoy-
lated alanine-rich C-kinase substrate (MARCKS) has 
been found to improve functional recovery after SCI 
in female mice; however, peptides do not always 
pass the blood-brain barrier and are easily degraded 
due to natural proteases and are excreted during 
kidney filtration. Therefore, the ED peptide cannot 
access the central nervous system to exhibit its ef-
fects if administered intravenously. Instead of inject-
ing the ED peptide into the bloodstream, we pro-
pose to find compounds that can pass the blood-
brain barrier in place of the ED peptide, improving 
treatment compatibility. To find such alternatives, we 

screened compound libraries via competitive en-
zyme-linked immunosorbent assay (ELISA) and iden-
tified five potential ED peptide mimetics—com-
pounds that mimic the structure and function of the 
ED peptide. We then used another competitive 
ELISA to verify their structural similarity to the pep-
tide. After performing toxicity tests to determine the 
appropriate concentrations of the mimetics to use in 
functional assays, we found that all five mimetics trig-
ger a significant increase in neurite length in neurons 
from female mice, but not male mice, when com-
pared to the vehicle control solution. Although more 
functional tests are necessary, these results suggest 
that these mimetics trigger ED peptide functions 
and may provide a more efficient treatment alterna-
tive for SCI.   

 

1 INTRODUCTION 
Spinal cord injury (SCI) is a detrimental con-

dition impacting 39 individuals per million in the 
USA that results in permanent impairment or loss of 
motor and neurological function.[5] There is evidence 
that triggering signal cascades mediates neurite out-
growth, cell migration, and synaptogenesis by tar-
geting function-proactive cell adhesion molecules, 
leading to an improvement of functional recovery 
and regeneration after SCI.[11] One such cell adhe-
sion molecule, neural cell adhesion molecule 
(NCAM) —a cell-surface molecule known to help neu-
rons stick to other cells or the extracellular matrix—
binds to extracellular sugar polymer, polysialic acid 
(PSA) (FIGURE 1).[7] PSA has several different functions 
in the mammalian nervous system, including cell mi-
gration, axon growth, central nervous system plastic-
ity, and regeneration—all of which are helpful in SCI 
recovery.[2,21] Given the benefits of PSA, we were in-
terested in identifying and characterizing its recep-
tors; of these, we chose to further analyze myristoy-
lated alanine-rich C-kinase substrate (MARCKS) due 
to its high concentrations in the hippocampus and 
spinal cord, which could prove helpful in developing 
treatments targeting SCI.[16] 

 The effector domain (ED) on MARCKS acts 
as the binding site for PSA through the cell, regulat-



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

ing the beneficial effects of PSA (FIGURE 1).[23] A syn-
thetic peptide (ED peptide) containing the same 
amino acid residues as the ED of MARCKS was pre-
viously used to verify the MARCKS-PSA interaction, 
but it was unexpectedly found to also trigger down-
stream effects on its own. The ED peptide triggers 
neurite outgrowth of neurons, increases functional 
recovery, and enhances phosphorylation levels of 
MARCKS in neurons and spinal cords in female mice 
but not male mice.[24] 

Although the ED peptide shows promising 
effects on SCI models, it cannot be administered in-
travenously because the blood-brain barrier pro-
tects the central nervous system from some pep-
tides. To allow for an intravenous treatment option 
for SCI using the MARCKS-PSA pathway, we are 
looking for ED peptide mimetics—compounds that 
mimic the structure and function of the ED peptide—

that also cross the blood-brain barrier. We hypothe-
sized compounds that are structurally similar to the 
ED peptide are also functionally similar to the ED 
peptide. The current study tests this hypothesis by 
identifying mimetics based on structural similarity to 
the ED peptide via biochemical assays, then evalu-
ates their effects on neurons to determine their func-
tional similarity to the ED peptide, including sex-spe-
cific outcomes. 
 

2 MATERIALS & METHODS 

ELISA SCREENING AND VERIFICATION OF ED PEPTIDE MIMETICS  

To identify potential mimetics, we screened for small 
organic compounds from the National Institute of 
Health Clinical Collection Libraries 1 and 2 (NIH 
CCL1 and NIH CCL2) and the Natural Compound Li-
brary (NCL) via competitive ELISA (FIGURE 2A). Onto 
wells of an ELISA plate, we coated 1 µg/mL of 
MARCKS antibody (MARCKS AB, Sigma Aldrich). As 
a negative control, we treated two wells with phos-
phate buffered saline (PBS). Wells were then incu-
bated overnight at 4oC and then washed with PBS to 
discard any loose antibodies that were not attached 
to the bottom of the well. Wells were then treated 
with blocking solution (5% bovine serum albumin 
[BSA] + 0.1% Triton X-100 in PBS) for one hour at 
room temperature (RT) to prevent any compounds 
or reagents from adhering to parts of the well that 
were not coated with MARCKS AB. After washing, we 
added individual compounds from the NIH CCL1, 
NIH CCL2, and NCL to the wells and incubated them 
at RT for 30 minutes. Biotinylated ED peptide 
(GenScript) was then mixed with the compounds in 
each well (final compound concentration = 20 µM; 
final peptide concentration = 5 µM) for one hour at 
RT. In this step, compounds compete with the pep-
tide for access to the MARCKS AB, hence the term 
“competitive ELISA.” After washing, wells were 
treated with streptavidin coupled to horseradish pe-
roxidase (SA-HRP, Jackson ImmunoResearch. 
Pierce™) at 1:5000 in 5% BSA plus PBS for 30 
minutes at RT. Streptavidin has a high affinity to bio-
tin, so SA-HRP specifically binds to the biotinylated 
peptide. Afterward, wells were washed, then treated 
with HRP substrate (0.1% O- phenylenediamine di-
hydrochloride [OPD, Thermo Fisher Scientific] + 

FIGURE 1: SCHEMATIC OF MARCKS-PSA INTERACTION. 

Extracellular PSA bound to NCAM binds to the effector do-
main (ED) of intracellular MARCKS through the cell mem-
brane. When the ED peptide is applied, it competes with 
endogenous MARCKS and causes PSA to dissociate from 
MARCKS, therefore initiating a signal cascade that leads to 
neurite outgrowth. 



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

0.1% hydrogen peroxide [H2O2] in OPD buffer). OPD 
reacts with HRP and H2O2 to produce an orange 
compound; the more peptide, the more SA-HRP, 
and the more orange the solution appears. Color 
can be quantified by measuring absorbance at 450 
nm with an ELISA reader (EL800; BioTek Instru-
ments) after stopping the reaction at 20 minutes with 
2.5 M sulfuric acid.  
 From this screen, we identified amiodarone, 
epigallocatechin, nonyloxytryptamine, sertraline, 
and tegaserod (Sigma Aldrich) as potential mimet-
ics. To verify these compounds, we repeated this 

procedure except we added varying concentrations 
(0, 1, 5, 10, 25, 50, 100, 200 µM) of the select com-
pounds from the libraries during the competition 
step to see if they inhibit the binding of the ED pep-
tide to MARCKS AB in a concentration-dependent 
manner. Mimetics were prepared by dissolving the 
powdered form in dimethyl sulfoxide (DMSO) to 
make 10 mM stocks which were diluted with PBS to 
the concentrations listed above. Tacrine, a com-
pound found during the screen to not have any ef-
fect on MACKS binding to the MARCKS AB, was 
used as a negative control. Tacrine also binds to an 

FIGURE 2: SCHEMATIC OF COMPETITIVE ELISAS. 

A) Screening compound libraries for MARCKS ED peptide mimetics. Compounds that are not structurally similar to the ED  
peptide will not bind to the MARCKS AB, therefore allowing the ED peptide to bind. Conversely, compounds that are struc-
turally similar to the ED peptide will bind to the antibody and block the ED peptide from binding. The peptide is detected 
via streptavidin bound to horseradish peroxidase and OPD. 
 

B) Verifying that mimetics imitate the ED peptide by seeing if they interact with the ED peptide- binding to site on PSA. At high 
concentrations of the mimetic, more PSA will bind to the compound, leaving less free PSA to bind to the peptide. At low 
concentrations of the mimetic, more unbound PSA will be able to bind to the immobilized peptide and remain in the wells 
for detection. PSA is detected via anti-NCAM primary antibody, secondary antibody coupled to HRP, and OPD. 



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

antibody that activates another cell adhesion mole-
cule, L1; since L1 and MARCKS are unrelated, this of-
fers further reason to use tacrine as a negative con-
trol.[11]  
 To determine if the verified mimetics also in-
hibit the interaction between the ED peptide to its 
binding partner PSA, we first incubated varying con-
centrations (0, 1, 5, 10, 25, 50, 100, 200 µM) of each 
mimetic with 20 µg/mL of colominic acid (PSA, 
Sigma Aldrich) at 4oC overnight. Then we coated 5 
µM biotinylated ED peptide on a streptavidin-coated 
plate (Thermo Fisher Scientific) for one hour at RT. 
Subsequently, unbound ED peptide was washed off 
with PBS and the mixed solution of PSA and small 
organic compounds were added to the wells to in-
cubate at RT for one hour (FIGURE 2B). Afterward, the 
wells were washed and incubated with 1:200 of anti-
PSA-NCAM (primary antibody 735, Thermo Fisher 
Scientific) in PBS for one hour at RT. Subsequently, 
wells were washed and incubated with 1:1000 of 
mouse-HRP (secondary antibody) dissolved in block-
ing solution at RT for 30 minutes. Lastly, wells were 
washed and treated with HRP substrate. After 10 
minutes, we stopped the reaction with sulfuric acid 
and read absorbance at 450 nm on the ELISA reader. 
 
CEREBELLAR GRANULE CELL CULTURE  

Cerebellar granule cells make up the largest popu-
lation of neurons in the mammalian brain and are rel-
atively simple in structure, making them an ideal 
model for in vitro neuronal cultures.[13] To obtain 
these cells, we removed cerebella from 6 to 8-day-
old mice that were euthanized in accordance with 
the IACUC protocol #: 09-051. To begin the culture, 
48-well plates are coated with 0.01% Poly-Lysine-L 
(PLL) for 30-60 minutes in the incubator (37°C). PLL 
is a chain of synthetic amino acids that helps cells ad-
here to the bottom of the well-plates. Then, PLL was 
aspirated off, and wells were washed with sterile dis-
tilled water and left to dry. Stocks of medium (con-
taining Neurobasal A, B-27, Penicillin/Streptavidin, 
BSA, Na-Pyruvate, L-Glutamine, Transferrin holo, In-
sulin, L-Thyroxine, and Na-Selenite) were prepared, 
filtered, and warmed in a 37ºC water bath before 
use. Once cerebella were removed using sharp for-
ceps, the meninges and blood vessels were cleaned 

off. Subsequently, each cerebellum was cut into 
pieces and put into test tubes of HBSS (Hank’s Bal-
anced Salt Solution). HBSS is a buffer that keeps cells 
in their preferred pH range and helps maintain high 
viability during short-term incubations. HBSS was 
then removed via an aspirator, and trypsin was 
added to the tissue for a 15-minute incubation in a 
37ºC water bath. Trypsin breaks down adhesive pro-
teins that help cells stick together. Cell cultures re-
quire seeding individual cells for optimal imaging 
and even treatment stimulation. Subsequently, tryp-
sin was carefully aspirated from each test tube, and 
tissue was then washed with HBSS. DNase was then 
added to each test tube to digest any DNA that 
leaked from damaged cells, which can form aggre-
gates and hinder dissociation. Cells were then disso-
ciated via pipette until there were no visible pieces 
of cerebella left. Dissociated cells were incubated 
with the DNase solution for 5 minutes in a 37ºC water 
bath and then diluted with HBSS before centrifuga-
tion at 200 g for 5 minutes at 4ºC. Centrifugation is a 
separation technique that uses centrifugal force to 
collect heavier particles in a solution (in this case, the 
cells) at the bottom of a container, therefore creating 
a cell pellet. Afterward, HBSS was aspirated off, and 
the cell pellet was resuspended in a pre-warmed 
medium. Cell solution was combined with fluoro-
phores (acridine orange and propidium iodide, Nex-
celom Bioscience) that stain dead and live cells dif-
ferent colors to count the cells. Initial viability and 
concentration of live cells were measured using the 
Cellometer Auto 2000 Cell Viability Counter. Cells 
from males and females were measured and cul-
tured separately.  
 
TOXICITY TESTS 

The cerebellar granule cell culture procedure de-
tailed above was carried out, separating male and 
female mice. After counting cells, cells from each sex 
were separately diluted to 500,000 cells/mL with a 
pre-warmed medium. Cells were seeded into 24 
wells (12 for male cells and 12 for female cells) on 
0.01% PLL-coated 48-well plates with 250 µL of 
500,000 cells/mL solution in each well and main-
tained at 37°C for 24 hours. Afterward, cerebellar 
granule cells were incubated with 0.1% DMSO as a 



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

vehicle control, 1, 10, and 100 µM of the mimetic for 
another 24 hours. For live imaging, propidium io-
dide and calcein-am solution (each 4 ng/mL) were 
first added to each well, and the plate was then incu-
bated (37°C) for 20-30 minutes before using the flu-
orescent microscope. AxioVision was used to control 
contrast and adjust the clarity of the images. Four im-
ages were taken per well. The experiment was per-
formed three times in triplicate for each compound 
(𝑛𝑛 = 36). 
 

NEURITE OUTGROWTH 

The cerebellar granule cell culture procedure de-
tailed above was carried out, subsequently diluting 
cells from each sex to 100,000 cells/mL with a pre-
warmed medium. Cells were seeded into 4 wells per 
treatment (two for males and two for females) on 
0.01% PLL-coated 48-well plates. Cells were imme-
diately stimulated with 0.1% DMSO for final concen-
trations in the wells of 0, 0.1, 1, 10, 100, and 1000 nM 
of each mimetic diluted in DMSO. One row of wells 
was left untreated to see if DMSO would affect neu-
rite outgrowth. Plates were then incubated for 24 
hours at 37°C. Each well was treated with 2.5% glu-
taraldehyde to fix cells and left to incubate for 30 
minutes at RT. Subsequently, the wells were washed 
with water. Staining solution (1% toluidine blue O, 
1% methylene blue in 1% borax) was added to the 
wells and left to incubate at RT for 30 minutes. Wells 
were then washed with water, and the plate was left 
to dry so images could be taken. Images were taken 
using AxioVision. Neurites were traced and meas-
ured using ImageJ. 
 

STATISTICAL ANALYSIS 

Statistical comparisons between groups were per-
formed by one-way ANOVA test using StatView for 
all experiments because each had more than two ex-
perimental groups. Subsequently, Fischer’s PLSD 
post-hoc test is used to determine the statistically 
significant variance between groups. According to 
Fischer’s PLSD test, asterisks in figures signify statis-
tically significant differences between groups 
wherein, ∗ 𝑝𝑝 < 0.05, ∗∗ 𝑝𝑝 < 0.01, ∗∗∗ 𝑝𝑝 < 0.001. Every 
experiment was performed three independent times 
and the averages and standard errors of the mean 
were calculated from all trials on Microsoft Excel. 

Schematics, graphs, and calculations were done with 
Microsoft Office. 
 

3 RESULTS 

FIVE COMPOUNDS INHIBIT THE BINDING OF ED PEPTIDE TO  
THE MARCKS ANTIBODY  

Our results show that epigallocatechin, amiodarone, 
sertraline, tegaserod, and nonyloxytryptamine in-
hibit the binding of the ED peptide to MARCKS AB 
in a concentration-dependent manner. At 25 µM and 
higher concentrations, all the mimetics inhibit the ED 
peptide from binding to the antibody significantly 
more than our negative control, tacrine, another 
small organic compound from the NIH CCL1  
(FIGURE 3).  

 
ED PEPTIDE MIMETICS BIND TO PSA  

To further verify the integrity of the structural similar-
ity between the mimetics and the ED peptide, we 
conducted a competitive ELISA to see if the mimet-
ics could inhibit the binding of PSA to the ED pep-
tide (FIGURE 2B). From this procedure, we determined 
that the compounds inhibit the binding of the ED 
peptide to PSA in a concentration-dependent man-
ner, and all compounds significantly inhibit the bind-
ing of PSA to MARCKS at six concentrations or more 
(FIGURE 4). 

 
THE FIVE MIMETICS ARE NONTOXIC IN CEREBELLAR GRANULE 

CELLS AT 1µM  

Before determining if the identified mimetics trigger 
ED peptide-mediated functions, we determined the 
cytotoxicity of the mimetics. In all five MARCKS ED 
peptide mimetics, concentrations of 1 µM are non-
toxic for cerebellar granule cells in both sexes. A 10 
µM concentration of epigallocatechin gallate, is also 
nontoxic (FIGURE 5). We define the toxic range to be 
any percent viability equal to or less than 50%. There 
is no apparent sex-specific difference in toxic ranges 
shown in the data. Based on the data shown in  
FIGURE 5, we suggest using a maximum of 1 µM con-
centration in live functional assays. Therefore, we 
chose seven concentrations ranging from 0 µM 
(DMSO) to 1 µM of each compound to stimulate the 
cerebellar granule cells in our neurite outgrowth as-
says.  



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

 

FIGURE 3: VERIFYING POTENTIAL ED PEPTIDE MIMETICS. 

Verifying epigallocatechin gallate, amiodarone, sertraline, tegaserod, and 5-nonyloxytryptamine as potential ED peptide mi-
metics. Error bars indicate standard error of the mean. (Three independent trials were carried out in triplicate, 𝑛𝑛 = 9). Asterisks 
signify statistically significant differences between the identified mimetics and the negative control tacrine wherein ∗ 𝑝𝑝 < 0.05, 
∗∗ 𝑝𝑝 < 0.01, ∗∗∗ 𝑝𝑝 < 0.001. (One-way ANOVA, 𝐹𝐹 = 63.39, 𝑝𝑝 < 0.0001). 

FIGURE 4: DETERMINING IF MIMETICS INHIBIT THE BINDING OF PSA TO ED PEPTIDE. 

Determining if epigallocatechin, sertraline, amiodarone, tegaserod, and nonyloxytryptamine inhibit PSA from binding to ED 
peptide. Error bars indicate standard error of the mean. (Three independent trials were carried out in triplicate, 𝑛𝑛 = 9). Asterisks 
signify statistically significant differences between the identified mimetics and the negative control tacrine wherein ∗ 𝑝𝑝 < 0.05, 
∗∗ 𝑝𝑝 < 0.01, ∗∗∗ 𝑝𝑝 < 0.001 (One-way ANOVA, 𝐹𝐹 = 12.512, 𝑝𝑝 < 0.0001).  

 



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

THE FIVE MIMETICS PROMOTE NEURITE OUTGROWTH IN FEMALE 

CEREBELLAR GRANULE CELLS AT NANOMOLAR CONCENTRATIONS 

Our first functional test was to determine whether ED 
peptide mimetics promote neurite outgrowth in fe-
male cerebellar granule cells and not males, as the 
ED peptide does. All five mimetics significantly stim-
ulated neurite outgrowth at 0.01-1000 nM, except 
for amiodarone which promoted neurite outgrowth 
at only 1-1000 nM (FIGURE 6). In addition, neurite out-
growth was observed only in female cerebellar gran-
ule cells, supporting the discovery that MARCKS pro-
motes neurite outgrowth in a sex-specific manner. 
There was no significant difference in neurite length 
between DMSO-treated and mimetic-treated male 
cerebellar granule cells (FIGURE 6). Nonyloxytrypta-
mine was the most effective mimetic, promoting the 
most neurite outgrowth at 10000 nM with an aver-
age neurite length of 48.6 µm (SEM 1.85 µm) com-
pared with the vehicle control, DMSO, with an aver-
age neurite length of 31.4 µm (SEM 0.77 µm). Epi-
gallocatechin, sertraline, and tegaserod were also 

effective compounds in promoting neurite out-
growth with average neurite lengths of 46.5 µm 
(SEM 1.43), 42.2 µm (SEM 1.38), and 41.8 µm (SEM 
1.27) at 1000, 100, and 1000 nM, respectively. Amio-
darone was the least effective mimetic in promoting 
neurite outgrowth with an average length of 41.5 µm 
(SEM 1.36) at 100 nM (FIGURE 6). 
 

4 DISCUSSION 
Our results show that nonyloxytryptamine, 

epigallocatechin, sertraline, tegaserod, and amioda-
rone mimic both the structure and function of the ED 
peptide. We determined structural similarity with 
competitive ELISAs and functional similarities by 
measuring neurite outgrowth. 

The identified ED peptide mimetics may 
prove to be better treatment options because they 
are not as easily degraded or blocked by the blood-
brain barrier as the ED peptide. Additionally, com-
pounds from the libraries that we screened have a 
history of use in human clinical trials and SCI studies.  
  

FIGURE 5: MEASURING NEUROTOXICITY OF MARCKS ED PEPTIDE MIMETICS IN CEREBELLAR GRANULE CELLS. 

Cerebellar granule cells were dissociated from 6 to 8- day-old mice, separated by sex and seeded onto PLL-coated plates. After 
24 hours, cells were treated with DMSO or 1 µM, 10 µM,  or 100 µM of each mimetic. Cell viability was measured by propidium 
iodide and calcein-am staining to take the ratio of live cells to total cells. The bar graphs show the average cell viability and error 
bars indicate standard error of the mean. (Four images were taken per well. Three independent trials were carried out in tripli-
cate, 𝑛𝑛 = 36). 



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

  

FIGURE 6: MEASURING NEURITE OUTGROWTH OF CEREBELLAR GRANULE CELLS TREATED WITH DIFFERENT CONCENTRATIONS OF ED PEPTIDE MIMETICS. 

Cerebellar granule cells were dissociated from 6 to 8- day-old mice, separated by sex and seeded onto PLL-coated plates. Cells 
were immediately treated with 0.1% of DMSO and each mimetic with final concentrations of 0 nM, 0.1 nM, 1 nM, 10 nM, 100 nM 
and 1000 nM. The bar graphs show the average neurite length and error bars indicate standard error of the mean (100 neurites 
were measured in each treatment per trial. Three independent trials were carried, 𝑛𝑛 = 300). Asterisks signify statistically significant 
differences between the identified mimetics and DMSO wherein ∗ 𝑝𝑝 < 0.05, ∗∗ 𝑝𝑝 < 0.01, ∗∗∗ 𝑝𝑝 < 0.001. (Nonyloxytryptamine, one-
way ANOVA, 𝐹𝐹 = 21.11, 𝑝𝑝 < 0.0001; epigallocatechin, one-way ANOVA, 𝐹𝐹 = 18.39, 𝑝𝑝 < 0.0001; sertraline, one-way ANOVA, 
𝐹𝐹 = 13.064, 𝑝𝑝 < 0.0001; tegaserod, one-way ANOVA, 𝐹𝐹 = 10.789, 𝑝𝑝 < 0.0001; amiodarone, one-way ANOVA, 𝐹𝐹 = 11.968,  
𝑝𝑝 < 0.0001). 



  ARESTY  RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE III 
 
 
 

Two of the other verified MARCKS ED peptide mi-
metics, tegaserod, and nonyloxytryptamine, are also 
PSA mimetics that facilitate nervous system repair 
and improve recovery after SCI in mice.[4,15] Epigallo-
catechin gallate (EGCG) is an active compound 
found in green tea that has been shown to pass 
through the blood-brain barrier.[9] In some regards, 
EGCG appears to be functionally similar to the ED 
peptide in that EGCG improves functional recovery 
after chronic and acute SCI and sciatic nerve in-
jury.[12,18,19,25] Additionally, the ED peptide and EGCG 
increase the phosphorylation levels of MARCKS in 
neurons.[6,27] EGCG also has neuroprotective, anti-in-
flammatory, and anti-edema effects after spinal cord 
and sciatic nerve injury and attenuates neuropathic 
pain.[1,3,8,14,20,22,26,28] 

While we have found that the ED peptide 
improves functional recovery after SCI in female 
mice, the molecular mechanisms underlying sex-
specific responses remain unclear. Therefore, ED 
peptide mimetics are not only beneficial in poten-
tially substituting the peptide as a form of treatment 
but might offer insight into how the ED peptide pro-
motes neurite outgrowth and improves functional 
recovery in female mice. 

In the future, we will test if the mimetics en-
hance MARCKS phosphorylation levels specifically 
in female but not male cerebellar granule cells. We 
predict that the ED peptide mimetics will be effective 
replacements for the ED peptide in recovery from 
trauma not only in SCI but also in other model sys-
tems of trauma in mammals, fundamentally improv-
ing recovery response∎  

 

5 ACKNOWLEDGEMENTS 
Special thanks to Dr. Thomas Theis and Dr. 

Melitta Schachner for their mentorship, support, and 
guidance. Additionally, many thanks to the W.M. 
Keck Center for Collaborative Neuroscience for the 
facilities and resources. This paper contains data 
submitted in several progress reports submitted to 
the Department of Cell Biology and Neuroscience at 
Rutgers University’s School of Arts and Sciences. The 
New Jersey Commission for Spinal Cord Research 
funded this work (CSCR18ERG015). 

 

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Monica Tschang (she/her) is a senior majoring in Cell Biology and Neuroscience in the School of 
Arts and Sciences. To explore her interests in the gut-brain axis and mental health advocacy, she is 
also double minoring in Psychology and Nutrition. With this undergraduate background, she is 
applying to neuroscience PhD programs to study the neurobiological basis of mental health disor-
ders. She started research for the MARCKS ED peptide mimetic project in the beginning of 2019 
under Dr. Melitta Schachner at the W.M. Keck Center for Collaborative Neuroscience and will con-
tinue this project for her honors thesis. For questions, feel free to contact her at:  
MAT361@SCARLETMAIL.RUTGERS.EDU 


