Common aspects between glaucoma and brain neurodegeneration
Introduction
Neurodegeneration, by definition, affects neuronal cell function and structure leading to the gradual loss of neurons in specific brain regions [1]. Neurodegenerative diseases, including Alzheimer’s (AD) and Parkinson’s (PD) diseases, are a heterogeneous group of chronic central nervous system disorders, that share common pathophysiologic features [2]. One common feature involves disease-specific misfolded proteins whose aggregation precedes clinical manifestations by many years [3]. These diseases are age-related and characterized by a progressive course and a slow, but constant, physical aggravation [4,5]. Neurodegeneration may lead to irreversible damage to cognitive, motor and behavioral functions, depending upon the sub-cerebral area of the brain that is affected. Environmental and genetic factors could affect neurodegenerative diseases development and progression; changes in mitochondrial DNA seems to be involved in the pathogenesis of both AD and PD [6,7]. There are also some rare genetic variants that contribute to neurodegenerative diseases that follow Mendelian laws and other forms of these diseases for which it is difficult to demonstrate inheritance. The purpose of this review is to examine common pathogenetic features that overlap between AD, PD, and primary open angle glaucoma (POAG).
Section snippets
Alzheimer’s disease
AD, also called Alzheimer’s dementia, is the most common of the neurodegenerative diseases in the elderly in which brain degeneration leads to a progressive and global decline in cognitive and intellectual functions [8]. AD accounts for about 50–75 % of all dementia types [9]. Except for rare cases, it manifests after the sixth decade of life, and its progression to the most severe stages can occur in approximately 10 years. The estimated prevalence of AD for individuals 65–74 years of age is
Parkinson’s disease
PD is a common neurodegenerative disorder that affects 1–2 individuals per 1000 of the population. Prevalence increases with age and is estimated to be 1% in the population over 60 years of age [19,20]. The number of people diagnosed with PD is estimated to increase by more than 50 % by 2030 [21]. The etiology of PD is unknown in most cases, although genetic risk factors and environmental or behavioral contributors have been suggested. Occupational exposures to pesticides or metals (e.g. lead)
Glaucoma
The eye is an extroflection of the brain; thus, glaucoma is a degenerative disease that affects the entire neuronal chain from the retinal ganglion cells to the visual cortex [30]. It is the second leading cause of blindness and the leading cause of global irreversible blindness. In 2013, the global number of people (aged 40–80 years) with glaucoma was estimated at 64.3 million. An increase of up to 76.0 and 111.8 million cases is expected by 2020 and 2040, respectively [31]. Men are more
Oxidative stress
Oxidative stress precedes the appearance of amyloid plaques and neurofibrillary tangles in the brain affected by AD. The accumulation of soluble oligomers of β-amyloid in the brain and cerebrospinal fluid of patients with AD stimulate an increase in reactive oxygen species formation and activation of N-methyl-d-aspartate channels thus leading to a rapid increase of the intracellular calcium loading [[47], [48], [49]]. Intracellular calcium overload leads neuronal cells into mitochondrial
Conclusions
According to the discussions above, it is more than clear that AD, PD and POAG share some common pathogenic mechanisms, primarily: oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis (summarized in Table 2). The final pathogenic step in all of these diseases is the apoptosis of neurons in specific nervous system regions: the medial temporal lobe of the brain and the limbic system in AD, the Substantia Nigra pars compacta motor neurons in PD and the retinal ganglion cells in
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