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NEUROPROTECTION
Overview of Neurodegenerative Diseases
Recent advances in understanding the biological processes of
neuronal cell death as well as improved methods for demonstrating therapeutic
effects in humans has led to the concept of pharmacological
neurocytoprotection. Accordingly, the search for drugs with
a neuroprotective effect has now became an active trend for
neuronal diseases such as Parkinson's disease (PD), Alzheimer's disease
(AD), Huntington's disease, amyotrophic lateral sclerosis or even multiple
sclerosis. The two most common and classical examples of neurodegenerative
diseases, AD and PD, are used here to highlight the scientific merits of our
project.
AD is the most common form of senile dementia affecting millions
of people worldwide (Alzheimer's Society).
The neuropathological hallmarks of AD include excessive accumulation of abnormal
tau filaments in neurofibrillary tangles, abundant deposits of β-amyloid in
senile plaques, and extensive neuronal degeneration. Although the cause of the
neuronal degeneration in AD is not known, recent studies revealed a possible
link between neuronal apoptic cell death and increased β-amyloid production.
It has further been shown that oxidative stress is linked to β-amyloid-mediated
neuronal cytotoxicity as it triggers and/or facilitates neurodegeneration
through a wide range of molecular events which eventually lead to neuronal cell
loss. Interestingly, antioxidants have recently been shown to have a
beneficial effect in neurodegenerative disorders, β-amyloid-induced
neurotoxicity
and oxidative stress in neuronal cells.
Antioxidants may thus emerge as one of the therapeutic strategies to treat β-amyloid-induced
neurotoxicity and improve neurological outcome in AD.
PD is a further example of typical neurodegenerative disorder and
is characterised by symptoms including rest tremors, postural instability, gait
abnormality, bradykinesia and rigidity (see
Parkinson's Disease Society). The
major pathological change of Parkinson's disease is the progressive loss of
dopaminergic neurons in the substantia nigra pars compacta. The nigral
vulnerability fits well with the strong oxidative stress observed in PD.
Excessive reactive oxygen species generation that is caused by increased
oxidative damage and reduced antioxidant level has been identified within the
degenerating substantia nigra of PD patients. Interestingly, neurotoxins
to dopaminergic neurons such as 6-hydroxydopamine (6-OHDA) which are routinely
used to induce experimental Parkinsonism are known to induce the
formation of free radicals, inflammatory processes and apoptosis. The toxicity
of such Parkinson-inducing agents can also be altered by antioxidants.
Our Research Strategy
We have already developed and used several in-house
bioassay screens for the identification of natural antioxidants. Our
natural products have been demonstrated to possess potent protective effects
against oxidative damage to biological molecules including DNA, as well as
cytoprotection in a variety of experimental conditions [see under
publication]. We are now further studying the effect of our
natural antioxidant medicinal plants and their metabolites through in
vitro models of AD and PD. Our procedures utilise tissue culture-based
neurotoxicity/neuroprotective studies with biochemical endpoint measurements
using colourimetric, flouresence, flow cytometeric and
electrophoresis analysis. Our overall strategy is to identify a
multifunctional drug candidate that works through one drug-multiple targets
principle. For Alzheimer's disease, for example, our ideal candidate is a
neuroprotective agent that acts through antioxidant mechanism,
overcomes the acetylcholine deficit through anticholinesterase effect and also
possesses antiamyloid properties.
Targeting Amyloid
β toxicity and neuroregeneration
mechanisms.See also below mechanisms related to Amyloid
β
formation and how it can be targeted by potential drugs. Click on the images, to
see exemplary review articles in the field. The image below and title are from
our exemplary article on monoterpenes that appeared in the journal cover of
"Molecules".
Click on the image to access the free article. We have numerous other examples
(see references below) and continue to look for novel drugs and mechanisms that
could be of interest in neurodegenerative diseases. We always welcome any
proposal for collaborations in this area.
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Exemplary publication:
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Bandiwadekar, A.,
Jose, J., Khayatkashani, M.,
HABTEMARIAM, S., Kashani, H.R.K.,
Nabavi, S.M. (2021). Emerging
novel approaches for the
enhanced delivery of natural
products for the management of
neurodegenerative diseases.
Journal of Molecular
Neuroscience - Published
on 25 October 2021. IF
3.444.
Abstract
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Annunziata, A.,
Sureda, A., Orphan, I.E.,
Battino, M., Arnone, A.,
Jim´enez-García, M., Capo´, X.,
Cabotj, J., Sanadgol, N.,
Giampieri, F., Tenore, G.C.,
Kashani H.R.K., Silva, A.S.,
HABTEMARIAM, S., Nabavi,
S.F., Nabavi, S.M. (2021).
The neuroprotective effects of
polyphenols, their role in
innate immunity and the
interplay with the microbiota.
Neuroscience and
Biobehavioral Reviews 128,
437-453.
Abstract
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HABTEMARIAM,
S. (2019). The Nrf2/HO-1 axis as
targets for flavanones:
Neuroprotection by pinocembrin,
naringenin and eriodictyol.
Oxidative Medicine and Cellular
Longevity 2019,
Article ID 4724920, 15 pages.
Full Text
or
PDF
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HABTEMARIAM, S. (2019).
Antioxidant and
anti-inflammatory mechanisms of
neuroprotection by ursolic acid:
Addressing brain injury,
cerebral ischemia, cognition
deficit, anxiety, and
depression. Oxidative
Medicine and Cellular Longevity
2019: Article ID
8512048, 18 pages.
Full Text
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HABTEMARIAM, S. (2019).
Natural Products in Alzheimer’s
Disease Therapy: Would Old
Therapeutic Approaches Fix the
Broken Promise of Modern
Medicines?
Molecules
24(8),
1519.
Full Text
or
PDF
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Shirooie, S., Nabavi, S.F.,
Dehpour, A.R., Belwal, T.,
HABTEMARIAM, S., Argüelles, S.,
Sureda, A., Daglia, M., Tomczyk,
M., Sobarzo-Sanchez, E., Xu, S.,
Nabavi, S.M. (2018).
Targeting mTORs by omega-3 fatty
acids: A possible novel
therapeutic strategy for
neurodegeneration?
Pharmacological Research
135, 37-48.
Abstract
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HABTEMARIAM,
S. (2018).
Molecular
pharmacology of rosmarinic and
salvianolic acids: Potential
seeds for Alzheimer’s and
vascular dementia drugs.
Int. J. Mol.
Sci.
2018, 19(2),
458.
FULL TEXT
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HABTEMARIAM, S. (2018). Iridoids
and other monoterpenes in the
Alzheimer’s brain: Recent
development and future
prospects. Molecules
23(1), 117.
Full Text
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Braidy,
N., Behzad, S., HABTEMARIAM, S.,
Ahmed, T., Daglia, M., Nabavi,
S.M., Sobarzo-Sanchez, E.,
Nabavi, S.F. (2017).
Neuroprotective effects of
citrus fruit-derived flavonoids,
nobiletin and tangeretin in
Alzheimer's and Parkinson's
disease.
CNS Neurol
Disord Drug Targets
16(4), 387-397.
Abstract
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Nabavi,
S.F., Khan, H., D'onofrio,
G., Šamec,
D.,
Shirooie,
S.,
Dehpour,
A.R., Castilla,
S.A.,
HABTEMARIAM,
S.,
Sobarzo-Sanchez,
E. (2017). Apigenin as Neuroprotective
Agent: of mice and men.
Pharmacological Research. In Press.
Abstract
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Elufioye,T.O., Berida,
T.I., Habtemariam S.*
(2017). Plants-derived
neuroprotective agents: Cutting the
cycle of cell Death through multiple
mechanisms.
Evidence-Based
Complementary and Alternative Medicine
2017 2017:3574012.
27 pages.
Full Text
Link or
PDF
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HABTEMARIAM, S. (2017). Protective
effects of caffeic acid and the
Alzheimer's brain: An update.
Mini
Review in Medicinal Chemistry
17(8), 667-674.
Abstract
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Degennaro, L.,
Zenzola, M., Laurino, A., Cavalluzzi1,
M.M., Franchini, C., HABTEMARIAM, S.,
Matucci,
R.,
Luisi, R.,
Lentini, G. (2017). 2-Arylazetidines as
ligands for nicotinic acetylcholine
receptors.
Chem. Heterocycl.
Compd., 53(3),
329–334.
Abstract
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HABTEMARIAM, S.
(2017).
Going back to the
good old days: The merit of crude plant
drug mixtures in the 21st
century.
International Journal of Complementary &
Alternative Medicine
6(2),
2017, 1-5.
Full Text
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Roselli, M., Cavalluzzi, M.M.,
Bruno, C., Lovece, A., Carocci,
A., Franchini, C., HABTEMARIAM,
S., Lentini, G. (2016).
Synthesis and evaluation of
berberine derivatives and
analogues as potential anti-acetylcholinesterase
and antioxidant agents.
Phytochemistry Letters
18,
150-156.
Abstract
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HABTEAMRIAM, S. (2016). The
Therapeutic Potential of
Rosemary (Rosmarinus officinalis)
Diterpenes for Alzheimer’s
Disease.
Evidence-Based Complementary and
Alternative Medicine,
Volume 2016 (2016),
Article ID 2680409, 14 pages.
Free Full Text Article
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HABTEMARIAM, S. (2016). Rutin as
a natural therapy for
Alzheimer’s disease: Insights
into its mechanisms of action.
Current Medicinal Chemistry
23(9), 860-873.
Abstract
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Nabavi,
S.F., HABTEMARIAM, S., Di
Lorenzo, A., Sureda, A.,
Khanjani, S., Nabavi, S.M.,
Daglia, M. (2016). Post-stroke
depression modulation and in
vivo antioxidant activity of
gallic acid and its synthetic
derivatives in a murine model
system. Nutrients
2016,
8(5),
248; doi:10.3390/nu8050248
(Open
Access).
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Nabavi,
S.F., Braidy, N., HABTEMARIAM,
S., Sureda, A., Manayi, A.,
Nabavi, S.M. (2016).
Neuroprotective effects of
fisetin in Alzheimer’s and
Parkinson’s Diseases: From
chemistry to medicine. Current
Topics in Medicinal Chemistry,
16(17),
1910-1915.
Abstract
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Nabavi, S.F., Braidy, N.,
Habtemariam, S., Orhan, I.E.,
Daglia, M., Manayi, A., Gortzi
O., Nabavi, S.M. (2015).
Neuroprotective effects of
chrysin: From chemistry to
medicine. Neurochemistry
International
90,
224-231.
Abstract
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Nabavi, S.M., HABTEMARIAM, S.,
Daglia,
M., Loizzo, M.R., Tundis, R.,
Nabavi,
S.F. (2015).
Neuroprotective effects of
ginkgolide B against ischemic
stroke.
Current Topics in Medicinal
Chemistry 15(21),
2222-2232.
Abstract
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Nabavi,
S.F., Sureda, A., HABTEMARIAM,
S.,
Nabavi,
S.M.
(2015).
Ginkgolide Rd and ischemic
stroke, a short review of
literatures.
Journal of Ginseng Research
39(4),
299-303.
Abstrac
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Nabavi, S.F., Nabavi, S.M.,
HABTEMARIAM, S., Sureda, A., Moghaddam, A.H., Latifi, A.M. (2013).
Neuroprotective effects of methyl-3-O-methyl
gallate against sodium fluoride-induced oxidative stress in brain of rats.
Cellular and Molecular Neurobiology
33(2), 261–267.
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HABTEMARIAM, S. (2011). The
therapeutic potential of Berberis
darwinii stem-bark:
quantification of berberine and
in
vitro evidence for
Alzheimer’s disease therapy.
Natural Product Communications
6(8),
1089-1090.
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