Acetyl-L-Carnitine in Parkinson’s Disease

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder that is estimated to affect approximately 1% of the population older than 65 years of age (deRijk et al., 2006; Saunders, 2000). PD was first described in 1818 by the British physician J. Parkinson. Before that date, no one had ever described the symptoms of this disease; so many researchers theorize that this pathology is the product of the English Industrial Revolution (Parris, 2000; Perlmutter, 2000). Some authors speculate that new neurotoxic contaminants produced by the industries can have been the cause of this chronic and progressive disease. PD is characterized by the progressive depletion of pigmented dopamine-containing neurons in the region known as the substantia nigra pars compacta and by the presence of intraneuronal aggregates called Lewy bodies (LBs), which are enriched in filamentous -synuclein and other proteins that are often ubiquinated (Lee & Trojanowsky, 2006). Approximately 80% of dopaminergic neurons in the substantia nigra are already irreversibly destroyed when the symptoms of PD becomes significantly visible. Depletion of dopamine causes dysregulation of the motor circuits that project throughout the basal ganglia (BG), resulting in the cardinal clinical manifestations of PD: bradykinesia (extreme slowness), tremor, rigidity, and postural instability. Consequently, patients experience increasing difficulty in daily living functions along the course of the disease. Additional neuronal fields and neurotransmitter systems are also involved in PD, including the locus coeruleus, the dorsal motor nucleus, the autonomic nervous system and the cerebral cortex. Consequently, noradrenergic, serotoninergic, and cholinergic neurons are also lost. These widespread neuronal changes led to complex and variable progressive nonmotor symptoms such as cognitive decline, sleep abnormalities, and depression which dominate the later stages of PD (Braak, 2003). In any case, PD is primarily a sporadic disorder and its etiopathogenesis is still not fully understood, but the recent discovery of genes associated with rare monogenic forms of the disease, together with earlier studies and new experimental animal models, has provided important and novel insight into the molecular pathways involved in disease pathogenesis (Wood-Kaczamar, 2006). Increasing evidence indicates that deficits in mitochondrial function, oxidative and nitrosative stress, accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system