PPARgamma Agonists in the Treatment of Human Diseases

This article discusses the use of PPARgamma agonists as therapeutics for the treatment of various human diseases. It explores their potential in Alzheimer's disease, neurological disease, respiratory disease, and chronic kidney disease. The article provides insights into the mechanisms of action and clinical trials conducted on animal models.

Ppargamma
agonists in the
treatment of human
diseases

Contents
INTRODUCTION...........................................................................................................................1
MAIN BODY...................................................................................................................................1
CONCLUSION...............................................................................................................................7
REFERENCES..............................................................................................................................8

INTRODUCTION
PPAR agonists are drugs which act upon the peroxisome proliferator-activated receptor.
They are used for the treatment of symptoms of the metabolic syndrome, mainly for lowering
triglycerides and blood sugar. These drugs are basically been used as the nuclear receptor in
order to enhance the health outcome of an individual. These drugs are basically been built up in
fat cells and is being used as lipids to reduce the resistance of insulin. This agonist is basically
in human is been encoded by the PPARG gene. These drugs were originally been made for the
disorders related to cholesterol. Currently they are been used in order to treat the syndrome
which are metabolic in nature. They are also been useful for lowering down the level of blood
sugar. These are basically been used by health care professionals for feature high triglycerides.
Present report will lay emphasis on the relevant literature related to the topic which is
Ppargamma agonists in the treatment of human diseases.
MAIN BODY
Article 1: PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease
As per the view of Gurula and et.al., (2016) it has been analysed that most of the older age
people are been suffering from Alzheimer’s. It is one of the most common causes of dementia.
Patient who is suffering from this disease faces symptoms such as continuous decline in
thinking. This disease basically hampers individual’s functional abilities and reducing their
quality of life. Various interventions can be used by nurses in order to cure this disease. Many
strategies may temporary improve the signs and symptoms. It has been analysed from the
research that PPARgamma agonists are been used as therapeutics in order to have cure and
treatment for the Alzheimer’s disease.
The nuclear receptor such as PPARgamma which are mainly been used for doing biological
actions such as having a control over the level of glucose and lipid metabolism so that
inflammation process can be reduced. These recpetors are mainly been used for suppressing
the gene expression which is inflammatory in nature. This can act as an attractive therapeutic
target in order to treat disease like Alzheimer’s. It will assist in enhancing the quality of life of an
individual who is been suffering from AD. There are now so many evidences available that
PPARgamma improvises memory and cognition part in patients suffering from Alzheimer’s. The
receptors are been tested on the animal model. PPARgamma has been one of the most
important therapeutic target for treating disease like AD. It helps in improvising the synaptic
function in the human body. There have been so many clinical trials that has provided with the
proof that PPARgamma can be used in improvising the cognitive and memory functions of
patients. This also assists in lowering down the expressions of gene who can be inflammatory in
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nature. It has also been analysed from the research that patients suffering from Alzheimer’s
having destroying memory and also they loosen their capabilities to think.
Article 2: PPARgamma as a therapeutic target to rescue mitochondrial function in
neurological disease
In accordance with Tugrul and et.al., (2016) neurological disease can include various type
of disease such as Alzheimer’s and other type of dementia. It can include cerebra-vascular
disease such as stroke, headache, migraine and other traumatic disorders which can lower
down the quality of life of individual. It has been analysed that PPARgamma is a ligand
activated transcription that can be used for keeping and controlling the mitochondrial function. It
has been analysed that in recent years there has been a keen interest of scientist in making use
of therapeutic strategies for curing various type of neurological disease. PPARgamma can be
used in doing the cellular differentiation which can assist in preventing cancer metastasis. It
assists in protecting the vascular organs and also keeping blood glucose level in control. It can
also be used for controlling the blood pressure level.
PPARgamma also plays major role in keeping the insulin level controlled in human body.
This has assisted in enhancing the health outcome of humans or patients who have been
suffering from various type of neurological disease. PPAR isoforms can be used in maintaining
and keeping in control the integrity level of the central nervous system. It has also been
analysed from the research that all PPAR’s are been activated by the fatty acids. PPAR
agonists can also be used as the drug for controlling the blood sugar level. In this the synthetic
agonists are been divided into the group of five. TZD was the first member to the family and was
been used in order to cure the diabetes. It has also been analysed that there are certain type of
side effects which can be faced when using PPARgamma as therapeutic strategy.
As per the view point of To, Wu and Loong, (2018) PPARgamma can also be used as the
recovery receptor after patient has gone through stroke. It has been analysed that stroke can
reduce the health outcome of an individual and can also reduce their quality of life. Recently,
15D-PGJ2 a natural PPARγ ligand decreased neuronal autophagy by decreasing the
expression of proteins LC3-II, Beclin 1, cathepsin-B, and LAMP1 after cerebral ischemia
reperfusion injury. It can also be used in order to treat disease such as ischemia. It has been
analysed that the clinical trial has been done on the rat model. It has also been analysed that so
many scientist in recent years as taking interest in development of the therapeutic strategies for
curing the various neurological disorders. This has assisted them in enhancing the health
outcome of patient and also helping them overcoming from the life threatening disease. It has
also been analysed that PPARgamma has been used for treating various other human disease
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such as obesity and type 2 diabetes. There are various evidences which have shown
development in the following field. This has assisted in enhancing the health outcome of
individuals suffering from this life threatening disease.
In the opinion of Hsu and et.al., (2017) neuropathic pain can be considered as one of the
major pain after someone has gone through spinal injury. In this molecular mechanism has
been used in order to treat the pain. It has been analysed that novel therapeutic target can be
used in order to cure the pain which has been derives because of the spinal cord injury. The
clinical trial of this has been done on the rat model. It has also been analysed that neurological
disorder can reduce the health outcome of an individual. Scientist are been working really hard
to provide therapeutic intervention in curing the human disease. They are been working on
development of the PPARgamma. In rats with neuropathic pain has also been seen with signal
related Kinase. Significantly reduce touch stimulus has also been seen in it. It has been
evaluated that PPARgamma can also be used in as the protective mechanism in neuro-
generative disease. In this the patient can go through various situations like stroke, brain
tumour, and other problems. These diseases can reduce the health outcome and quality of life
of individual. It has also been analysed that the effects of PPARgamma has been noted in the
rats. It has shown an improvement in the survival rate. Neuro-generative diseases cause
paralysis and also shorten down the life span of an individual or patient who has been going
through this type of disease. It has been analysed that various therapeutic interventions has
been used and been developed in order to cure most of the human disease.
In the view point of Weinstein, INTEKRIN THERAPEUTICS (2017) PPARgamma has also
been used as therapeutic intervention for curing the Huntington’s disease. It is one of the most
common disorders related to brain which lay serious impact on thinking capability of an
individual. In this patient can face various type of emotional problems and can also have low
thinking capabilities. Most of the people who are going through Huntington’s disease are mainly
adults. This disease can reduce the health outcome of an individual. It basically appears for
persons in their thirties and forties. Various type of therapies are been used in order to manage
the signs and symptoms related to this disease. There are also potential benefits of the
PPARgamma for treating the neurological disease. These receptors has reduce the signs of
oxidative stress which has been faced by those individuals who are been suffering from the
neurological disease. PPARgamma has assisted in overcoming the problem related to this. It
has also been analysed that it has also reduce the expression of genes which is been required
during the inflammatory process. The clinical trial was been done on mouse model. The
treatment was also been done with pioglitzone reduced levels of brain.
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Article 3: PPAR
‐γ agonists as therapy for diseases involving airway neutrophilia
As per the view point of Schmitz and et.al., (2017) PPAR gamma agonists is also been
used as the therapy for the diseases consisting of airway neutrophilia. This can be recognised
as the chronic feature for disease like Chronic obstructive pulmonary disease. It has been
analysed that smokers are more prone to getting the lung disease in comparison with no n
smokers. The various signs and symptoms related to disease includes shortness in breathe,
coughing, sneezing. This disease can reduce the health outcome of an individual who has been
suffering from COPD. It has been analysed that PPAR gamma is been used as therapeutic
intervention to cure the chronic symptom like airway neutrophilia. It has also been analysed
from the research that PPAR agonist is been used as the extent for airway inflammation. It is
been used to reduce the gene expression related to inflammation process. PPAR ligands are
been tested on lungs of the mouse. In this the author has provided the details that if peroxisome
proliferator activated repeater same as it has opened in lung of mouse then this compound can
be used as the potential therapy for the treatment of various type of respiratory disease.
Moreover it has also been analysed that PPAR-gamma is also useful for treating various other
type of human disease such as Type 2 diabetes, neurological disease and many other.
It has been analysed that these receptors can be used to cure respiratory disease. This
therapy can also beneficial for treating various respiratory diseases. They are working towards it
to explore the use relatively quickly. The exact mechanism for the actions related to PPAR-
gamma is also not been known. The authors has realised that PPAR-gamma is beneficial for
reducing the risk related to airway neutorphilia and other type of respiratory disease. This
therapeutic intervention can be used to enhance the health outcome of individual suffering from
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various type of disease such as COPD. It has also been analysed from the research that PPAR-
gamma is been used to cure type 2 diabetes without having any significant side effects. This
intervention has no side effects like any other pharmaceutical intervention. This also has
assisted in curing various type of neurological disease. In this to test the effectiveness of PPAR-
gamma has been done by doing clinical trial on lungs of mouse. It has show significant better
effects when doing the clinical trial. It has also been analysed that these receptors has less side
effects. They are more engaged in enhancing the health outcome of patients suffering from
various diseases such as respiratory and other type of lung disease. There are various
evidences which have shown development in the following field. This has assisted in enhancing
the health outcome of individuals suffering from this life threatening disease. It has also been
analysed that PPAR-gamma has additional anti-inflammatory activities to that of a steroid when
dosed using this protocol. This has assisted the health care professionals in reducing the risk factors
related to airway neutrophilia. It has also been analyzed that this disease is basically associated with
COPD where patients can face various symptoms such as shortness in breathe, coughing and
sneezing reducing the health well-being of service user.
Article 4: PPARγ and Its Agonists in Chronic Kidney Disease
In accordance with Elshazly and Soliman, (2019) chronic kidney disease means that kidney
of the patient is been damaged and unable to filter the blood. This disease is been considered
as chronic as it happens slowly over a period of time. It has also been analyzed from the
research that chronic kidney disease can also cause other health related problems and issues.
It has also been analyzed that if an individual is suffering from the long term with the problem of
chronic kidney disease can suffer from other severe problem such as renal failure. It can reduce
the quality of life and health outcome of patient suffering from chronic kidney disease.
Medication can be provided to patients in managing symptoms. The signs and symptoms
related to this disease are been developed slowly. Sometimes even no symptom related to
chronic kidney disease has been analyzed and evaluated.
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Chronic kidney disease has become global health care issue. PPAR-gamma has been
involved in playing the anti-biotic role. This ligands were been used for curing the hepatitis
cardiac and kidney problems. The clinical trial has been done on mice model and has also
shown significant positive impact that PPAR-gamma can be used for curing the chronic kidney
disease. PPAR-gamma is also been used as the receptors to reduce the inflammation which
causes kidney disease. Inflammation can be taken as one of the major cause in decline of
kidney and also for the decline in functioning of kidney. This can be used for the energetic
modification that can assist in curing the kidney disease. These receptors like PPAR-gamma
can be used as therapeutic intervention for treating chronic kidney disease and also can be
used in curing renal failure. This can assist in developing the health outcome of patients who
are suffering from this type of disease.
It has also been analyzed from the research that PPAR-gamma is most important receptors
for the renal glucose control. It increases beneficial adipokines which is useful for keeping in
control the renal formation of glucose. The clinical trial was been done on rat model and has
showed significant positive impact. It has also been analyzed that PPAR-gamma is useful for
the filtration process related to glucose. They are also essential for re-absorption and also for
the transportation of glucose in kidney. This therapeutic intervention can be useful for curing this
disease without any side effects. All PPARs have been detected in rodent and human kidney,
including glomeruli, medullary collecting duct, and pelvic urothelium. It has also been analyzed
from the research that chronic kidney disease can reduce the health and well-being of patients
who are been suffering from it. It has also been analyzed that this agonists is also been useful
for slowing down the progression related to podocyte failure. This has also assisted in
improvising health outcome of an individual. It has also been useful for reducing the risk and
vulnerabilities related to the chronic kidney failure.
Article 5: PPAR-gamma and Its Role in Cardiovascular Diseases
As per the view of Mangoni And et.al., (2017) cardiovascular disease are becoming one of
the major health issue. It has been analyzed that there are various problems related to heart
that can be faced by an individual who also reduces their health outcome. It has been analyzed
that they can face problems like heart stroke, pain in chest and many others. There are various
signs and symptoms related to cardiovascular diseases like patient can face chronic pain in
chest, loss in appetite, inability to breathe. The cardio vascular diseases can also be life
threatening. It can reduce the health outcome of patients and can lay negative impact on their
well being. It has also been analyzed from the research that PPAR-gamma is been used for
treatment and curing process of various cardiovascular disease. It has also been used for the
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resistance of insulin which has been seen in the disease such as type 2 diabetes. The patients
suffering from diabetes are at high risk of cardio vascular disease, obesity and insulin
resistance. These receptors such as PPAR-gamma are been used for reducing down the
inflammatory process which can give rise to various type of diseases. They are also been used
for curing hypertension. These receptors are been used as the insulin resistance and also can
be used for filtering out the blood glucose level. It can reduce the risk related to cardio-vascular
disease. It can enhance health and well-being of an individual.
CONCLUSION
From the above study it has been summarized that PPAR-gamma has been used as the
agonists for treating various type of human disease such as type 2 diabetes, renal failure, and
neurological disorder. It has also been analyzed that this receptors has also been used for
chronic kidney failure. The authors has realised that PPAR-gamma is beneficial for reducing the
risk related to airway neutorphilia and other type of respiratory disease. It has been analysed
that novel therapeutic target can be used in order to cure the pain which has been derives
because of the spinal cord injury. The clinical trial of this has been done on the rat model. It has
also been analysed from the research that this therapeutic intervention has less side effects
than the other interventions. This has been useful for enhancing quality of life of individual. It
has also been analysed that these receptors are also been tested so that many other human
disease can also be cured. PPAR-gamma has been useful for lowering down the risk related to
various type of human disease. It has assisted in enhancing the health outcome of individual
suffering from various lungs, respiratory or other type of disease. It has been useful for
improvising quality of life.
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REFERENCES
Books and Journals
Hsu, W.C.J. and et.al., 2017. PPARgamma agonists rescue increased phosphorylation of
FGF14 at S226 in the Tg2576 mouse model of Alzheimer's disease. Experimental
neurology, 295, pp.1-17.
To, K.K., Wu, W.K. and Loong, H.H., 2018. PPARgamma agonists sensitize PTEN-deficient
resistant lung cancer cells to EGFR tyrosine kinase inhibitors by inducing
autophagy. European journal of pharmacology, 823, pp.19-26.
Weinstein, D., INTEKRIN THERAPEUTICS Inc, 2017. PPAR gamma agonists for treatment of
multiple sclerosis. U.S. Patent 9,539,249.
Gurula and et.al., 2016. In silico screening of potent ppargamma agonists among natural
anticancer compounds of Indian origin. Asian J Pharm Clin Res, 4, pp.320-24.
Tugrul, I. and et.al., 2016. Effects of a PPAR-gamma receptor agonist and an angiotensin receptor
antagonist on aortic contractile responses to alpha receptor agonists in diabetic and/or
hypertensive rats. Cardiovascular journal of Africa, 27(3), p.164.
Schmitz, J.M. and et.al., 2017. PPAR‐gamma agonist pioglitazone modifies craving intensity
and brain white matter integrity in patients with primary cocaine use disorder: a double‐
blind randomized controlled pilot trial. Addiction, 112(10), pp.1861-1868.
Mangoni, M. And et.al., 2017. A PPAR-gamma agonist protects from radiation-induced intestinal
toxicity. United European gastroenterology journal, 5(2), pp.218-226.
Elshazly, S. and Soliman, E., 2019. PPAR gamma agonist, pioglitazone, rescues liver damage
induced by renal ischemia/reperfusion injury. Toxicology and applied pharmacology, 362,
pp.86-94.
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