The cutting edge: apoptosis and therapeutic opportunity - Artificial Cells, Cell Engineering and Therapy - page 125

There is mounting evidence that the dopaminergic neurons in the substantia
nigra are under immense oxidative stress; leading to the multiple misfolding of
proteins such as parkin and a-synuclein, which form fibrils constituting the lewy
body, a pathological hallmark of PD (Schapira et al., 1990; Bucciantini et al.,
2002).

5.6 Therapeutics
Currently, dopamine antagonists, monoamine oxidase inhibitors, anti-excitotoxic
drugs are being studied and developed to treat PD patients. A lot of research is
also focused on the use of antioxidants, which will help abate the deleterious
effects of oxidative stress on dopaminergic neurons. Cell transplantation therapy
is also one of the approaches to ameliorate the symptoms of neuro-degenerative
diseases in animal models (BjÈ rklund and Stenevi, 1979; Date et al., 1996;
Borlongan et al., 1998; Saporta et al., 1999). The treatment proposes the use of
fetal neuronal cells, which is a huge difficulty from the ethical point of view as
well as the availability of fetus. However, recent studies have indicated the use of
more readily available cells such as genetically engineered cells, encapsulated
cells and different cell lines (Bankiwicz et al., 1993; Freed, 1993; Hammang et
al., 1995; Date et al., 1996; Raymon et al., 1997; Schinstine et al., 1997).
Neurons are post-mitotic tissues. It is difficult to study the biochemical
mechanisms of neurodegenerative diseases due to the lack of availability of
human neurons. Human teratocarcinoma (NT2N) and human neuroblastoma
(SH-SY5Y) cells have been used as neuronal models to study neuronal functions.
They resemble human primary neurons and like them, elaborate processes that
differentiate into dendrites (Pleasure et al., 1992, 1993).
Differentiated human teratocarcinoma (NT2-N) cells have been shown to
survive and integrate within the host brain after transplantation and help in
function recovery in animal models of stroke, PD and Huntington's disease
(Borlongan et al., 1998; Hartley et al., 1999; Muir et al., 1999; Sandhu et al.,
2003).

5.7 Advances in development of neuro-protective

agents

Coenzyme Q 10 (Fig. 5.5) is an essential electron and proton carrier that functions
in the production of biochemical energy in aerobic organisms. Coenzyme Q 10
also has antioxidant and membrane-stabilizing properties that serve to prevent
the cellular damage that results from normal metabolic processes. It is a highly
hydrophobic, lipid-soluble molecule with a quinone ring attached to an isoprene
side chain.
Coenzyme Q 10 has been shown to have protective effects in lymphocytes,
skin cells and heart diseases (Singh et al., 1999; Tomasetti et al., 1999; Hoppe et