SIGNIFICANCE OF NERVE

GROWTH FACTOR

Submitted to kuhs university in partial fulfiment of the

Requirement for the award of degree of

BACHELOR OF PHARMACY

Submitted by
ABHIRAM AJITH
150091664

MARCH 2019

NATIONAL COLLEGE OF PHARMACY

MANASERRY,MUKKAM

KOZHIKODE-673 602,KERALA
 CERTIFICATE

This is to certify that the dissertation entitled “Significance of nerve growth

factor” is a record of bonafide work conducted by Mr.ABHIRAM AJITH” under my
direct supervision and guidance in National college of pharmacy,Manassery,Mukkam
pharmacy,Manassery,Mukkam,Kozhikode

Dr.AKASH MARATHAKAM

Senior Lecturer
Dept. of Pharmaceutical Chemistry
National college of pharmacy
Manassery,Mukkam
Calicut.

Place:Manassery
Date:

AKNOWLEGMENT
It is always difficult to list comphrensive all those whose invaluable influence has been
felt in the successful completion of my project.
I express my sincere gratitude and indebtness to my teacher and
guide Dr.AKASH MARATHAKAM,senior lecturer,National college of pharmacy for
his immense support and guidance extended to me throughout my work.
I am grateful to Dr.M.K UNNI KRISHNAN ,principal of National college
of Pharmacy,Manassery,Mukkam,Kozhikode for his advice and valuable suggestions.
My whole hearted thanks to all the teachers of National college of Pharmacy for their
help and encouragement in completion of project
I express my acknowledgment to all my friends for their technical support and valuable
advice.
I am also offering a thousand praise to the almighty who granted inspiration and
guidance to complete this project work
At last but not the least I extended my regards to my family for their prayer and constant
support during my studies.

ABHIRAM AJITH

Final year B.pharm

National college of pharmacy
Kozhikode
 CONTENTS

 Introduction
 Structure
 Functions
 Mechanism of action
 History
 Clinical significance
 Yogic connection
 Interactions
 Formulation
 Ways to increase NGF
 Gene Location
 NGF in the treatment of Depression
 Conclusion
 Reference

INTRODUCTION
● Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide
primarily involved in the regulation of growth, maintenance, proliferation, and
survival of certain target neurons.

●It is perhaps the prototypical growth factor, in that it was one of the first to
be described.

●Since it was first isolated by Nobel Laureates Rita Levi-Montalcini and

Stanley Cohen in 1956, numerous biological processes involving NGF have
been identified, two of them being the survival of pancreatic beta cells and the
regulation of the immune system.

● Nerve growth factor (NGF) is required for the survival of developing

sympathetic and sensory neurons. In the absence of NGF, these neurons
undergo protein synthesis-dependent apoptosis. Ten years have gone by since
the first reports of specific genes being upregulated during NGF deprivation-
induced cell .

●Nerve growth factor improves spatial learning and restores hippocampal

cholinergic fibers in rats withdrawn from chronic treatment with ethanol

●Nerve growth factor (NGF) is the most understood growth factor in pain
sensitivity and inflammatory hyperalgesia.

Structure
NGF is initially in a 7S, 130-kDa complex of 3 proteins - Alpha-NGF,
Beta-NGF, and Gamma-NGF (2:1:2 ratio) when expressed. This form
of NGF is also referred to as proNGF (NGF precursor). The gamma
subunit of this complex acts as a serine protease, and cleaves the N-
terminal of the beta subunit, thereby activating the protein into
functional NGF.
The term nerve growth factor usually refers to the 2.5S, 26-kDa beta
subunit of the protein, the only component of the 7S NGF complex that
is biologically active (i.e. acting as signaling molecules).
FUNCTIONS

●Neuronal proliferation

●Proliferation of pancreatic beta cells

●Regulation of the immune system

●Ovulation

●Romantic love
Proliferation of pancreatic beta cells

There is evidence that pancreatic beta cells express both the TrkA and
p75NTR receptors of NGF. It has been shown that the withdrawal of
NGF induces apoptosis in pancreatic beta cells, signifying that NGF
may play a critical role in the maintenance and survival of pancreatic
beta cells.

Regulation of the immune system

NGF plays a critical role in the regulation of both innate and acquired
immunity. In the process of inflammation, NGF is released in high
concentrations by mast cells, and induces axonal outgrowth in nearby
nociceptive neurons. This leads to increased pain perception in areas
under inflammation. In acquired immunity, NGF is produced by the
Thymus as well as CD4+ T cell clones, inducing a cascade of
maturation of T cells under infection.

Ovulation
NGF is abundant in seminal plasma. Recent studies have found that it
induces ovulation in some mammals e.g. “induced” ovulators, such as
llamas. Surprisingly, research showed that these induced animals will
also ovulate when semen from on-schedule or “spontaneous”
ovulators, such as cattle is used. Its significance in humans is
unknown. It was previously dubbed ovulation-inducing factor (OIF) in
semen before it was identified as beta-NGF in 2012.
Romantic Love

Recent studies found that the concentration of NGF in the blood

plasma is significantly higher in individuals who have been in a
romantic relationship with another person for less than 12 months [227
(14) pg/ml], than those who are either not in a romantic relationship
[149 (12) pg/ml] or have been in one for more than 12 months [123
(10) pg/ml].
NGF can indirectly stimulate the expression of Adrenocoticotrophic
hormone(ACTH) in the hypothalamic-pituitary-adrenal axis (HPA) by
increasing vasopressin secretion. ACTH binds to the MC2 receptor in
the zona fasciculata of the adrenal cortex, and stimulates secretion of
the stress hormone cortisol.[12] This rapid increase of cortisol in the
blood plasma can induce feelings of euphoria, which may explain the
initial "rush" of falling in love. Studies show that ACTH can in turn
stimulate NGF secretion in both the cerebral cortex and the
hypothalamus. It is possible that this NGF-ACTH interaction may form
a recursive cycle, maintaining the "feeling of love" for a certain length
of time. Because NGF modulates nerve plasticity, neurogenesis, and
axonal outgrowth, this may form permanent memories associating the
loved one with the feeling of love during the course of the cycle.
However, it has been shown that cortisol, whose secretion is directly
upregulated by ACTH, shows inhibitory effects over NGF expression in
the cerebral cortex. This may be the cause of the eventual
deterioration of NGF levels after 12 months. It may also explain why
plasma NGF levels were significantly lower in individuals who have
maintained a long-lasting romantic relationship beyond 12 months,
than those who weren't in a romantic relationship at all.
Mechanism of action
NGF binds with at least two classes of receptors: the tropomyosine
receptor kinase A (TrkA) and low-affinity NGF receptor
(LNGFR/p75NTR). Both are associated with neurodegenerative
disorders.
When NGF binds to the TrkA receptor, it drives the homodimerization
of the receptor, which in turn causes the autophosphorylation of the
tyrosine kinase segment. This leads to the activation of PI 3-kinase,
ras, and PLC signaling pathways. Alternatively, the p75NTR receptor
can form a heterodimer with TrkA, which has higher affinity and
specificity for NGF.
Studies suggest that NGF circulates throughout the entire body via the
blood plasma, and is important for the overall maintenance of
homeostasis.

Neuron survival
Binding interaction between NGF and the TrkA receptor facilitates
receptor dimerization and tyrosine residue phosphorylation of the
cytoplasmic tail by adjacent Trk receptors. Trk receptor
phosphorylation sites operate as Shc adaptor protein docking sites,
which undergo phosphorylation by the TrkA receptor .Once the
cytoplasmic adaptor protein (Shc) is phosphorylated by the receptor
cytoplasmic tail, cell survival is initiated through several intracellular
pathways.
One major pathway leads to the activation of the serine/threonine
kinase, Akt. This pathway begins with the Trk receptor complex-
recruitment of a second adaptor protein called growth factor-receptor
bound protein-2 (Grb2) along with a docking protein called Grb2-
associated Binder-1 (GAB1). Subsequently, phosphatidylinositol-3
kinase (PI3K) is activated, resulting in Akt kinase activation. Study
results have shown that blocking PI3K or Akt activity results in death of
sympathetic neurons in culture, regardless of NGF presence.[17]
However, if either kinase is constitutively active, neurons survive even
without NGF.
A second pathway contributing to cell survival occurs through
activation of the mitogen-activated protein kinase (MAPK) kinase. In
this pathway, recruitment of a guanine nucleotide exchange factor by
the adaptor and docking proteins leads to activation of a membrane-
associated G-protein known as Ras.[7] The guanine nucleotide
exchange factor mediates Ras activation through the GDP-GTP
exchange process. The active Ras protein phosphorylates several
proteins, along with the serine/threonine kinase, Raf. Raf in turn
activates the MAPK cascade to facilitate ribosomal s6 kinase (RSK)
activation and transcriptional regulation.
History

Rita Levi-Montalcini and Stanley Cohen discovered NGF in the 1950s

while faculty members at Washington University in St Louis. However,
its discovery, along with the discovery of other neurotrophins, was not
widely recognized until 1986, when it won the Nobel Prize in
Physiology or Medicine.
Studies in 1971 determined the primary structure of NGF. This
eventually led to the discovery of the NGF gene.
NGF is abundant in seminal plasma. Recent studies have found that it
induces ovulation in some mammals.
Clinical significance

Nerve growth factor prevents or reduces neuronal degeneration in

animal models of neurodegenerative diseases and these encouraging
results in animals have led to several clinical trials in humans. NGF
promotes peripheral nerve regeneration in rats. The expression of NGF
is increased in inflammatory diseases where it suppresses
inflammation. NGF appears to promote myelin repair. Hence NGF may
be useful for the treatment of multiple sclerosis. NGF could also be
involved in various psychiatric disorders, such as dementia,
depression, schizophrenia, autism, Rett syndrome, anorexia nervosa,
and bulimia nervosa.
Dysregulation of NGF signaling has also been linked to Alzheimer's
disease. Connective tissue cells genetically engineered to synthesize
and secrete NGF and implanted in patients' basal forebrains reliably
pumped out NGF, which enhanced the cells’ size and their ability to
sprout new neural fibers. The treatment also rescued vulnerable cells,
even if they already showed the trademark signs of Alzheimer’s
pathology. In some patients, these beneficial effects lasted almost 10
years after the treatment. Even patients who died responded positively
to the therapy. Even pathological cells with protein clumps in their cell
bodies and surroundings extended their fibers toward the NGF source,
maintained a healthy size and activated pro-survival signals that
boosted their stress resilience. Two other patients received direct
injections of modified viruses containing the NGF gene directly to their
basal forebrains. This allowed the gene to express longer in the brain.
Neurotrophins, including NGF, have been shown to affect many areas
of the brain, including areas that are related to Rett syndrome, bipolar
disorder, and Alzheimer’s disease. Stress and/or anxiety are usually a
precipitating factor in these disorders and affects levels of NGF,
leading to impaired cognitive functioning.
This impaired cognitive functioning can be seen in patients with
Schizophrenia. In treatment of schizophrenia, NGF levels are
increased in patients using atypical antipsychotic medication, but not in
patients using typical antipsychotic medications. Patients using atypical
medications usually report improved cognitive performance compared
to those using typical antipsychotics. Higher NGF levels from the
atypical antipsychotic medications may underlie the reduction in
negative symptoms of Schizophrenia relative to typical antipsychotics.

NGF has been shown to restore learning ability in rats recovering from
induced alcoholism.

Rett syndrome and autism often show similar signs early in life, such
as slowing development and intellectual disability. One distinguishing
factor is that low levels of NGF have been found in the cerebral spinal
fluid of children with Rett syndrome compared to children with Autism
who have relatively normal to high levels Pharmaceutical therapies
with NGF-like activity can be effective in treating Rett syndrome,
including better motor and cortical functioning as well as increased
social communication.
Impairment of neuroplasticity and altered levels of neuro-trophins are
involved in bipolar disorder. NGF has been found to be decreased
overall in bipolar disorder patients. More specifically, while in a manic
state NGF is especially low. This leads to elevated or irritable mood
with increased energy and decreased need for sleep while in a manic
state. This decreased NGF may serve as a biological marker when
assessing the present state of a bipolar disorder patient. When bipolar
disorder patients were treated with lithium, their NGF concentrations
increased in the frontal cortex, limbic forebrain, hippocampus, and
amygdala.
An increase in cortical and subcortical NGF has been found in patients
with Alzheimer’s disease. Alzheimer’s is a neurodegenerative disease
with which dysregulation of NGF signaling has also been linked,
causing impaired retrograde transport of NGF to certain areas of the
brain. This impairment may be caused by an atypical production or use
of receptors in the brain. Stimulating NGF receptors via NGF infusion
has been shown to increase blood flow and verbal episodic memory.
These improvements have been longer lasting than other treatments
for Alzheimer’s.
Also, NGF has been shown to play a role in a number cardiovascular
diseases, such as coronary atherosclerosis, obesity, type 2 diabetes,
and metabolic syndrome. Reduced plasma levels of NGF and BDNF
have been associated with acute coronary syndromes and metabolic
syndromes. NGF is known to have insulinotropic, angiogenic, and
antioxidant properties. NGF suppresses food intake.

NGF has also been shown to accelerate wound healing. There is

evidence that it could be useful in the treatment of skin ulcers and
cornea ulcers.
In some gynecological diseases, an elevated prostaglandin E2 is
thought to stimulate production of NGF which contributes to the
perception of pain and increased inflammation in endometriosis.
Monoclonal antibodies against NGF have been used in clinical trials to
modulate pain. One of these is tanezumab. An other one is
fulranumab.
 Yogic Connection

• Nerve growth factor may contribute to increased longevity and

mental capacity.
• Centenarian Rita Levi-Montalcini took a daily solution in the form of
eye drops, and has stated that her brain is more active now than it
was four decades ago.
In 2014, Sundaravadivel Balasubramanian and coworkers at Medical
University of South Carolina showed that NGF level is elevated in people who
performed a single 20-minute yoga session involving om-chanting and
thirumoolar pranayama, when compared to a control group.
Interactions

Nerve growth factor has been shown to interact with TrkA and p75NTR
(LNGFR).
It has recently been suggested that NGF expression may be stimulated by
dehydroepiandrosterone (DHEA). DHEA may also act as an agonist of both
TrkA and p75NTR and activate the pathways of NGF, demonstrating
neurotrophic activities similar to that of NGF.
Due to the increasing cases of neurodegenerative diseases in recent
years, the eventual goal of nerve repair is very important. One
approach for achieving a neuronal cell induction is by regenerative
pharmacology. Nerve growth factor (NGF) and brain derived
neurotrophic factor (BDNF) are neurotrophins that play roles in
neuronal development, differentiation, and protection. On the other
hand, dehydroepiandrosterone (DHEA) is a neurosteroid which has
multiple actions in the nervous system. DHEA could be an important
agent in regenerative pharmacology for neuronal differentiation
during tissue regeneration. In a study, scientists investigated the
possible role of DHEA to modulate NGF and BDNF production. The
in vivo level of neurotrophins expression was demonstrated by
ELISA in rat harvested brain cortex. Also neurotrophins expression
after DHEA treatment was revealed by the increased neurite
extension, immunostaining, and BrdU labeling in rats. Anti-NGF and
anti-BDNF antibodies were used as suppressive agents on
neurogenesis. The results showed that NGF and BDNF are
overproduced after DHEA treatment but there is not any
overexpression for NT-3 and NT-4. Also DHEA increased neurite
extension and neural cell proliferation significantly. Overall, DHEA
might induce NGF and BDNF neurotrophins overproduction in
cortical neurons which promotes neural cell protection, survival, and
proliferation.
Nerve growth factor (NGF) is the most important target-derived
trophic factor for basal forebrain cholinergic neurons (BFCNs) [.
These are small proteins, which share more than 50% sequence
homology. These factors could enhance survival, proliferation, and
differentiation of postmitotic neurons . It is known that they could
increase in neuronal numbers and neurite outgrowth . So it is
important to find molecules that promote overproduction of the
neurotrophins. In a study, scientists focused to understand the
induction of NGF and BDNF through dehydroepiandrosterone
(DHEA) as a pharmacological agent.
DHEA is an adrenal, glial, and neuronal derived steroid. Although
DHEA is produced by the human adrenal, it is not produced by the
rodent adrenal. It has multiple actions in the nervous system but no
specific receptor has been reported for this neurosteroid. DHEA
could be an important agent in neuronal differentiation during
development or could provide a microenvironment for stem cells
neurogenesis . DHEA is present in very low concentrations in the
blood of rats; however, the rodent brain may be able to make it from
its precursor pregnenolone . In adults, DHEA could act as
anticorticosteroid molecule on in vitro cultures of neurons . It
protects hippocampal cells from oxidative stress and antagonizes the
neurotoxic effects of corticosterones in primary cultures of neurons .
The successful regeneration of the neurons is dependent on the cells
survival and their progenitors proliferation . From the point that
DHEA (its sulfate form; DHEAS) is the most frequent neurosteroid
in the human body, we hypothesized that DHEA may influence the
NGF and BDNF production to induce neurogenesis and/or neuronal
survival.
Formulations

• Marketed formulations are also available

 How to Increase Nerve Growth
Factor (NGF)

Lifestyle modifications to Increase NGF

●Social Enrichment early in life – Mice reared in a more social environment

had higher NGF in selected brain areas (hippocampus and hypothalamus) as
adults .

●Yoga (even a single 20 minute session)

●Stress reduction– Chronic mild stress decreased the concentration of

NGF in the rat hypothalamus .

●Exercise: Low Intensity Resistance Training (R), Treadmill exercise

●Falling in love

●Intense Exercise: Allergic and neuro-immune disorders such as ALS

tend to occur more frequently among athletes. NGF increases with
stressors and allergies in humans and after physical exercise in animals.
A study of blood levels of NGF in olympic athletes showed significantly
higher levels of NGF than controls

Diet
 Alcohol (when taken with Fish Oil)
 Cooke Mushroom
 Cordyceps Mushroom
 Gac
 Green Tea
 Lion's Mane Mushroom (my favorite)
 Maitake Mushroom
 Panus Giganteus Mushroom
 Royal Jelly
 Super Coffee (regular coffee will not increase NGF expression)

Hormones
 ACTH (upregulating NGF expression in the brain) R
 Alpha MSH R
 DHEA R R
 Estrogen P R
 Melatonin R
 Oxytocin (in diabetic rats) R
 Progesterone R

Supplements
 ALCAR
 ALCAR-Arginate
 Alpha-GPC
 Ashitaba
 Astragalus
 Bupleurum
 Butyrate
 DHA
 EGCG
 Forskolin
 Genistein
 Ginkgo Biloba
 Gotu Kola
 Huperzine A
 Idebenone
 Lithium
 Magnolia Bark
 Milk Thistle
 Nardosinone/Valerian Root
 Nicotine
 Noopept
 Phosphatidylserine
 Polygala tenuifolia
 PQQ
 Quercitin
 Rehmannia
 Rosemary
 Sulforaphane
 Uridine (with Choline + DHA)
 Vitamin A
 Vitamin D3 (with Forskolin, results doubled, but is influenced by blood sugar)
 Yohimbine
 Zinc (for memory improvement, vitamin A must be sufficient)
 Ziziphus jujuba

Drugs
 2-deoxy-d-glucose
 NGF eye-drops
 Selegiline
GENE LOCATION

Gene for the production of ngf is located in chromosome

1.
NGF IN THE TREATMENT OF DEPRESSION

Nerve growth factor (NGF), a regulator of the development of the neurologic

system, was initially discovered by Cohen and Levi-Montalcini, who won the
1986 Nobel Prize for this amazing discovery.Since first being discovered in
1979, NGF has been proved to play a variety of roles in different areas, such
as neurology,angiogenesis,7immunology,urology,and others. In recent
decades, some researchers have tried to investigate the possible role of NGF
in the psychiatric area.
Major depressive disorder (MDD) is one of the most severe psychiatric
diseases in the world. It leads to massive financial burdens, increases the risk
of suicide, and is complicated with other physical comorbidities. The etiology
of MDD is believed to be heterogeneous, and the pathophysiology of MDD
remains unclear to this day. It is believed that neurobiological alteration and
neurodegeneration may play a role in the pathophysiology of MDD.
In recent studies, some links between the neurobiological characteristics of
NGF and MDD were found. The first link was the role of NGF in subjects’
response to stress – both emotional and physiologic stress. This could be
explored in two aspects. The first line of evidence is derived from theoretical
inference. NGF has been proved to be a modulatory factor in the
hypothalamic–pituitary–adrenal (HPA) axis and has been shown to have an
effect on the maintenance of the neuroendocrine and immune systems.In
addition, abnormality of HPA axis function in MDD has been reported in
many studies.The second line of evidence is derived from animal studies,
which have revealed decreasing levels of NGF in specific brain areas of
different mouse models, including anxiety vulnerability, stress-induced
illness, learned helplessness, and threatening treatment.All of those mouse
models are believed to represent forms of the depression models. Another link
is the alteration of NGF in different emotional states. For example, Emanuele
et al found higher levels of NGF in subjects “in love” who were intensely
focusing attention on a preferred individual and who were emotionally
dependent on and craving emotional union with this beloved person. Similar
alterations were seen in different emotional states.The third link is the
correlation of NGF levels in the peripheral environment and the central
nervous system (CNS). This link is especially important because it supports
the rationale for researchers investigating peripheral NGF levels rather than
directly investigating NGF levels in the CNS. Some studies have indicated
that NGF could cross the blood–brain barrier (BBB) under special conditions,
although not so readily.This is important because in clinical settings, it is
difficult for clinicians to directly check NGF levels in the human CNS, but
they can easily investigate peripheral NGF levels, through blood drawing.
As mentioned above, there are increasing studies and articles discussing the
relationship between NGF and depressive disorders. Repeated studies have
compared the differences in peripheral NGF levels in patients with MDD and
healthy controls (HCs),and others have investigated the effect of different
treatments on the peripheral NGF levels in patients.However, many of the
results have been conflicting and have brought confusion to the direction of
further study. Among studies investigating the differences in peripheral NGF
levels in patients with MDD and HCs, some revealed that NGF protein levels
were significantly lower in the patients than in HCs.Other reports have
suggested that NGF levels were significantly higher in patients than in HCs or
that there was no significant difference between these two groups in terms of
NGF protein or messenger (m)RNA levels.At the same time, some other
studies have discussed the changes before and after adequate treatment in
patients with MDD; however, almost all the results in these studies revealed
no statistically significant difference before and after treatment.These
inconsistent findings might have resulted from various confounding factors,
such as differences in study design, ethnicity, physical illness, age, sample
size, sex distribution, medical histories, length of illness, previous
psychotropic exposure, severity of disease, or sample sources (plasma, serum,
or whole blood). In addition, the correlation between peripheral NGF protein
levels and clinical parameters still remains unclear.
Conclusion

• Since its discovery several decades ago, nerve growth factor (NGF) has
been found to play roles in different areas, such as neurology,
endocrinology, and immunology.

• There is some evidence linking NGF and psychiatry, including the role of
NGF in subjects’ response to stress, the alteration of NGF in different
emotional states, and the penetration of NGF across the blood–brain
barrier under specific conditions.

• Besides the estensive literature available, we still need further

exploration of the dynamic changes in peripheral NGF during the
disease course, and specific studies investigating the correlation of NGF
in the peripheral and CNS environments
References
● Aloe, L. and Levi-Montalcini, R., 1979. Nerve growth
factor induced overgrowth of axotomized superior
cervical ganglia in neonatal rats. Similarities and
differences with NGF effects in chemically axotomized
sympathetic ganglia. Archives italiennes de
biologie, 117(4), p.287.

●Lee, R., Kermani, P., Teng, K.K. and Hempstead, B.L.,

2001. Regulation of cell survival by secreted
proneurotrophins. Science, 294(5548), pp.1945-1948..

●Chen, Y.W., Lin, P.Y., Tu, K.Y., Cheng, Y.S., Wu, C.K. and
Tseng, P.T., 2015. Significantly lower nerve growth factor
levels in patients with major depressive disorder than in
healthy subjects: a meta-analysis and systematic
review. Neuropsychiatric disease and treatment, 11,
p.925.

●Mondal, A.C. and Fatima, M., 2018. Direct and indirect

evidences of BDNF and NGF as key modulators in
depression: role of antidepressants treatment.
International Journal of Neuroscience, pp.1-14.

●Salles, F.H.M., Soares, P.S.M., Wiener, C.D., Mondin, T.C.,

da Silva, P.M., Jansen, K., de Mattos Souza, L.D., da Silva,
 R.A. and Oses, J.P., 2017. Mental disorders, functional
impairment, and nerve growth factor. Psychology
research and behavior management, 10, p.9.

●Chen, Y.W., Lin, P.Y., Tu, K.Y., Cheng, Y.S., Wu, C.K. and
Tseng, P.T., 2015. Significantly lower nerve growth factor
levels in patients with major depressive disorder than in
healthy subjects: a meta-analysis and systematic
review. Neuropsychiatric disease and treatment, 11,
p.925.
●Riikonen, Raili, and Hannu Kokki. "CSF nerve growth
factor (ß-NGF) is increased but CSF insulin-like growth
factor-(IGF-1) is normal in children with tuberous
sclerosis and infantile spasms." (2019).(Conference)
● Kolli, S., Bojic, S., Ghareeb, A.E., Kurzawa‐Akanbi, M.,
Figueiredo, F.C. and Lako, M., 2019. The Role of Nerve
Growth Factor in Maintaining Proliferative Capacity, Colony‐
Forming Efficiency, and the Limbal Stem Cell
Phenotype. Stem Cells, 37(1), pp.139-149.