throughout life, their aggregates gradually accumulate as we age. These aggregates form distinct and observable structures in the brain which generally known as amyloid deposits in the brain. Furthermore, some form of mutation increase the chance of misfolding in proteins which is the case in the genetic or familial case of NDs [22].
Though the mechanism is not clear, it has been proven that deposits of misfolded proteins are known to be neurotoxic and able to cause apoptosis in neuronal cells. There are however mechanisms that are able to inhibit aggregation of proteins and protect the CNS from such danger. Examples of these include the chaperones that are able to bind to misfolded protein and cause them to fold into their native structure, …show more content…
Amyloid deposits consist of aggregates containing 40 or 42 amino acid residues. Aggregate of 42 residue are more likely to form and are also overproduced when there is a genetic mutation [22]. In rare cases of early onset of PD which runs in some families, mutations in a synaptic protein called α-synuclein that was originally identified from smaller peptides isolated in amyloid-containing fractions of AD brains are observed [51, 52]. The α-synuclein proteins are synaptic proteins that are able to aggregate and form fibrils and are the major component of the Lewy body lesions; characteristic of PD as well as certain cases of AD and several other neurodegenerative conditions [53]. In the HD, mutation of huntingtin, a cytoplasmic protein, leads to it aggregation and form inclusions in cell nucleus in the brain. These aggregations, alongside the interaction of mutated huntingtin protein with regulatory caspases, are believed to be component of the pathophysiology of HD [54]. In the case of ALS, it is the SOD that aggregates. There is evidence to suggest that the accumulation of SOD aggregate may lead to inflammation and neurotoxicity
Though the mechanism is not clear, it has been proven that deposits of misfolded proteins are known to be neurotoxic and able to cause apoptosis in neuronal cells. There are however mechanisms that are able to inhibit aggregation of proteins and protect the CNS from such danger. Examples of these include the chaperones that are able to bind to misfolded protein and cause them to fold into their native structure, …show more content…
Amyloid deposits consist of aggregates containing 40 or 42 amino acid residues. Aggregate of 42 residue are more likely to form and are also overproduced when there is a genetic mutation [22]. In rare cases of early onset of PD which runs in some families, mutations in a synaptic protein called α-synuclein that was originally identified from smaller peptides isolated in amyloid-containing fractions of AD brains are observed [51, 52]. The α-synuclein proteins are synaptic proteins that are able to aggregate and form fibrils and are the major component of the Lewy body lesions; characteristic of PD as well as certain cases of AD and several other neurodegenerative conditions [53]. In the HD, mutation of huntingtin, a cytoplasmic protein, leads to it aggregation and form inclusions in cell nucleus in the brain. These aggregations, alongside the interaction of mutated huntingtin protein with regulatory caspases, are believed to be component of the pathophysiology of HD [54]. In the case of ALS, it is the SOD that aggregates. There is evidence to suggest that the accumulation of SOD aggregate may lead to inflammation and neurotoxicity