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376 Current Drug Metabolism, 2015, 16, 376-388
Application of Proteomic Tools in Modern Nanotechnological Approaches Towards
Effective Management of Neurodegenerative Disorders
Ashraf Ali
1
, Ishfaq Ahmed Sheikh
1
, Zeenat Mirza
1
, Siew Hua Gan
2
, Mohammad Amjad Kamal
1,3
,
Adel M. Abuzenadah
1,4
, Ghazi A. Damanhouri
1
and Ghulam Md. Ashraf
1,*
1
King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia;
2
Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelan-
tan, Malaysia;
3
Enzymoic, 7 Peterlee Pl, Hebersham, NSW 2770, Australia;
4
KACST Technology Innovation Cen-
ter in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
Abstract: Neurodegeneration is the progressive loss of structure or function of neurons leading to neuronal death,
usually associated with ageing. Some of the common neurodegenerative disorders include Alzheimer’s disease,
Parkinson’s disease, Creutzfeldt-Jakob disease, and Huntington’s disease. Due to recent advancements in high-
throughput technologies in various disciplines such as genomics, epigenomics, metabolomics and proteomics, there
has been a great demand for detection of specific macromolecules such as hormones, drug residues, miRNA, DNA,
antibodies, peptides, proteins, pathogens and xenobiotics at nano-level concentrations for in-depth understanding of
disease mechanisms as well as for the development of new therapeutic strategies. The present review focuses on the management of age-
related neurodegenerative disorders using proteomics and nanotechnological approaches. In addition, this review also highlights the me-
tabolism and disposition of nano-drugs and nano-enabled drug delivery in neurodegenerative disorders.
Keywords: Disposition, nano-applications, nano-drugs, nano-techniques, nanotechnology, neurological disorders, proteomics.
1. INTRODUCTION
The term neurodegeneration is generated by a combination of
two different words, ‘neuro’ meaning ‘nerve cells’ and ‘degenera-
tion’ meaning ‘progressive damage’; and can be applied to various
conditions that result in continual loss of neuronal structure and
function finally leading to neuronal death [1]. Common neurode-
generative disorders (NDDs) include Alzheimer’s disease (AD),
Parkinson’s disease (PD), Creutzfeldt-Jakob disease, fronto-
temporal dementia and Huntington’s disease [2]. Progressive accu-
mulation and aggregation of proteins like tau, -synuclein and amy-
loid- (A) have been reported to be involved in the gradual devel-
opment of various NDDs [3, 4]. Unfortunately, to our knowledge,
there is no single drug available that can halt or even slow down the
progress of brain degeneration caused by NDDs. Apart from ad-
verse effects on human health, NDDs have been reported to exhibit
significant associations with other chronic diseases like cancer,
diabetes and cardiovascular diseases [4-8]. Many different ap-
proaches have been proposed and utilized to develop cure of these
chronic diseases [9-13], but full proof treatment options are still
obscure. This calls for an urgent need to develop accurate and in-
formative diagnostic tests as well as effective therapeutics for the
devastating health burdens which could be based on new techno-
logical advancements such as proteomics and nanotechnology.
Proteomics deals with the identification, quantification and
characterization of the total protein content present at a given time
to help understand life at molecular level by development of novel
therapeutic agents and diagnostic tools to provide insights for new
biotechnological advancements [14]. The skills, experimental
*Address correspondence to this author at the King Fahd Medical Research
Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi
Arabia; Tel/Fax: +966552679568;
E-mails: gashraf@kau.edu.sa, ashraf.gm@gmail.com
approaches and technological platforms supporting proteomics
research are rapidly evolving [15]. Therefore, the application of
novel qualitative and quantitative nanotechnological findings in the
study of NDDs at different levels of neuronal circuit have the po-
tential to help elucidate the biochemical pathogenesis of neurode-
generation and aid in the discovery of new biomarkers [16, 17].
The field of nanotechnology is an amalgamation of chemistry,
engineering, biology and medicine [18]. According to the National
Cancer Institute (NCI), nanotechnology includes the utilization of
various technologies such as nanoarrays, protein arrays, nanopore
technology, nanosensors and immunoassays involving nanoparti-
cles (NPs) which have great potential to transform modern medi-
cine in terms of diagnosis and treatment of diseases [19]. Analyses
at nanolevel concentrations promise better efficiency, rapidity, low
running cost and small sample volume requirement, all of which are
indispensible in the latest platforms of proteomics, glycomics and
metabolomics [20]. Therefore, the future potential lies in pro-
teomics-based discovery and detection of nano-enabled biomarkers.
A rational combination of proteomics with nanotechnology offers
greater hope for therapeutic advances that could ameliorate NDDs
[21, 22].
Recent advancements in high-throughput genomics and pro-
teomics technologies can aid scientists to develop nano-analytical
techniques capable of detecting hormones, drug residues, RNA,
DNA, antibodies, peptides, proteins, pathogens and xenobiotics at
nanolevel concentrations [23]. New methods and techniques such as
protein conjugation with wheat germ agglutinin, cationic moieties
(cationization), antibodies and nanogels are being developed for
targeted-delivery of drugs and biomacromolecules to the central
nervous system (CNS) for treatment of NDDs [24, 25]. Since the
use of a number of approaches in understanding the pathogenesis
and management of NDDs has not yielded promising results so far,
this review focuses on the potential usage of modern proteomics
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