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
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
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.
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.
HABTEAMRIAM, S. (2016). The
Therapeutic Potential of
Rosemary (Rosmarinus officinalis)
Diterpenes for Alzheimer’s
Evidence-Based Complementary and
Volume 2016 (2016),
Article ID 2680409, 14 pages.
Free Full Text Article
HABTEMARIAM, S. (2016). Rutin as
a natural therapy for
Alzheimer’s disease: Insights
into its mechanisms of action.
Current Medicinal Chemistry
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
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,
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
Nabavi, S.M., HABTEMARIAM, S.,
M., Loizzo, M.R., Tundis, R.,
Neuroprotective effects of
ginkgolide B against ischemic
Current Topics in Medicinal
S.F., Sureda, A., HABTEMARIAM,
Ginkgolide Rd and ischemic
stroke, a short review of
Journal of Ginseng Research
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
HABTEMARIAM, S. (2011). The
therapeutic potential of Berberis
quantification of berberine and in
vitro evidence for
Alzheimer’s disease therapy.
Natural Product Communications
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