Current concepts of neurodegenerative diseases began to develop over a century ago 1. A direct correspondence between the formation of the neuropathological lesions and the degenerative process has emerged for many years 1.
Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and sclerosis, are characterized by the progressive loss of specific neuronal cell populations and are associated with protein aggregates. A common feature of these diseases is the extensive evidence of oxidative stress, which can be responsible for the dysfunction or neuronal death 2.
Neurodegenerative diseases are generally age dependent disorders 3. Since the demographic attributes and dynamics of the world population are irreversibly increasing the percentage of the elderly, the number of patients afflicted with neuro-degenerative diseases has been increasing 4. Neuro-degeneration is complex in its pathophysiology. It includes hundreds of neurology disorders 5. Below, we listed the most common ones.
1. Amyotrophic Lateral Sceloris and Multiple Sclerosis
The two main forms of sclerosis are amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). ALS was first described by Charcot in 1874 7. It is characterized by a rapid and progressive degeneration of motor neurons in the brain and spinal cord 6. It gradually leads to bulbar, respiratory and limb weaknesses 8 as well as paralysis and premature death (within 2 to 4 years 8) 6. Overall, the prevalence of ALS is low, but incidence increases with age, showing a peak between 55 and 75 years 6. Neuropathological features of ALS include intracellular accumulations and perikaryal inclusions of neurofilament and intracellular inclusions such as Bunina bodies and Lewy body–like cytoplasmic inclusions 6. It was reported that although most cases of ALS are sporadic, familial cases have been identified. In most of these cases, mutations in the SOD1 and ALS2 genes were identified 3 6.
Progression of neurological dysfunction is also a characteristic of multiple sclerosis. Indeed, MS is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that engenders a cumulative and irreversible damage of the CNS 8. MS is considered as the most common demyelinating disease of humans in developed countries and affects mainly young adults 9. This disease can have two forms: relapsing-remitting and secondary-progressive forms 10. Furthermore, large proportion of patients will mostly progress to a secondary-progressive form 10. The relapsing-remitting course can affect patients between 15 and 50 years old 9. The pathological hallmark of MS is the plaque, a white-matter demyelination area 9. This disorder is accompanied by inflammation in an early stage and astrogliosis at a later stage 9. It was reported that MS affects around 2.3 million adults worldwide and leads to changes in the central nervous system that often result in impaired physical and cognitive functions 11. In addition, about 350 000 cases of MS in the USA were reported, resulting in more than 3000 deaths per year 9. Most of the therapeutic approaches to MS aim at suppressing the immune system to control the inflammatory process that causes the demyelination and axonal damage 8. Nevertheless, the available treatments are partially effective in the progressive phases of the disease 8.
2. Alzheimer’s Disease
In 1907, Alois Alzheimer described for the first time the neuritic plaques and neurofibrillary lesions associated to the disease that was subsequently named after him 1. Alzheimer’s disease (AD) is considered as the most common neurodegenerative disorder 1. Statistical data suggests that by 2025, in the United States, more than 10 million cases of Alzheimer’s disease will be identified 3. Furthermore, the World Alzheimer Report 2016 estimated the presence of 46.8 million people worldwide with AD-related dementia in 2015 and predicted that the number of patients will be almost tripled by 2050 12. Thus, this disorder represents one of the major global health crises of the 21st century 12. The progression of Alzheimer’s disease is directly correlated to the deposition of amyloid-β peptides in the human brain as mature fibrils according to the amyloid cascade hypothesis 12.
3. Parkinson’s Disease
Parkinson’s disease (PD) was first discovered by James Parkinson in 1817 1. It is the second most common neurodegenerative disorder after Alzheimer’s disease 1. PD was reported to affect 1–2% of the general population over the age of 65 1. In addition, almost 50% of people who are 85 years old have at least one symptom of parkinsonism 3. PD is characterized by three cardinal symptoms: muscle rigidity, bradykinesia and resting tremor, in addition to postural instability, a mask-like facial expression, festinating gait and cognitive impairment 1.
The main neuropathological particularity of the disease is eosinophilic, round cytoplasmic inclusions in the form of Lewy bodies 1. These inclusions were first described in 1912 by Friederich Lewy 1. They are mostly concentrated in the substantia nigra 1. The degeneration of the substantia nigra and the reduction in dopamine cause most of the motor abnormalities in PD 1. It was reported that most cases of PD are idiopathic, however, genetic (mutations in α-synuclein gene, and PARK3 and PARK4 loci) and environmental (oxidative damage) causes are considered as risk factors of PD 1.
4. Huntington’s Disease
Huntington disease (HD) is caused by the degeneration of neurons in the basal ganglia followed by the cortical regions 6. This results in involuntary movements (chorea), psychiatric symptoms and dementia. Its prevalence is similar to that of ALS 6. Approximately 90% of HD cases are hereditary and transmitted in an autosomal dominant way 6. It was reported that all cases of Huntington’s disease (HD) are non-sporadic and are caused by expanded polyglutamine repeats 3.
On the one hand HD is different from the other previously listed diseases as it is attributable to a defect in a single gene 6. Furthermore, they are similar to the previously listed diseases in that they are expressed as neurologic deficits in adulthood,even if the expression of the mutant gene products in the central nervous system begins early in life 3. Childhood forms of HD are known to be due to large expansions of the causative triplet repeats 3.
4. Batten’s Disease
Batten’s disease, also known as neuronal ceroid lipofuscinoses (NCL) 13, are inherited lysosomal storage diseases 14. It was first described in 1903 by Frederick E. Batten 15.
It is one of the most common neurodegenerative disorders of childhood 13 16. NCL is clinically characterized by blindness, dementia, seizures, inevitable death 13. NCL is shown as an autosomal recessive mode of inheritance and is divided in four groups 14: the infantile type (INCL), the late infantile type (LINCL), the juvenile type (JNCL), and the adult type (Kufs) 13 17 18. The INCL variant is due to mutations in the palmitoyl protein thioesterase gene or CLN I 13. The JNCL is caused, mostly by deletions in the novel gene, CLN 13. One of the variant LINCL subtypes maps to chromosome 13 13 18
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