A brief idea about Neurodegeneration & the related diseases
The term Neurodegeneration means neuron related gradual loss of function or structure, which can even lead up to the death of neurons. The neuron related diseases like ALS, Huntington’s, Alzheimer’s and Parkinson’s are the causes of neurodegenerative processes. Many researches have proved that these diseases are related to one another. With the advanced researches, it has been established that different therapeutic treatments can ameliorate many of the diseases in a simultaneous way.
Many parallels are found in between varied neurodegenerative disorders that include induced cell death and typical type of protein assemblies. Neurodegenerative symptoms is noticeable in different levels of neuronal circuitry that range from molecular to systemic
Neurodegenerative disorders & their interlinks
Genetic mutations are the causes of different neurodegenerative diseases. Most of these genetic mutations are found in completely unrelated genes. Common features are found among the mutated genes in many of the different diseases that is a CAG nucleotide triplet’s repeat. These types of diseases are known to be Polyglutamine dieses. Amino acid glutamine is encoded by CAG. If CAG gets repeated, it results in a PloyQ / polyglutamine tract. The symptoms of these types of diseases are known as ploiyglutamine diseases.
Plyglutamine diseases: These types of diseases cause dominant pathogenesis. Due to various reasons toxic properties are formed by the extra residues of glutamine. This includes degradation pathways, irregular protein folding, other cellular proteins’ abnormal interactions and sub-cellular localizations. Various animal models are used for PolyQ studies, because of its uniquely defined trigger that is known as repeat expansion. Non-human primates, mice, fruit flies and varied types of worms have been used for undertaking extensive researches on it. It must be carefully noted that only the mammalian data is mostly needed for the drugs’ FDA approval. This necessitates bulk researches on mice. However, other animals like Drosophila and C. elegans are also primarily used for investigating about the equivalent mammalian gene.
Because of the expansion of the PloyQ and CAG trinucleotide tract, nine neurodegenerative diseases are inherited. To exemplify two of them are Spinocerebellar ataxias and Huntington's disease. Diseases like polyglutamine-repeat cause various types of neurodegenerative disorders. Each disease’s genetic differs from other and in many of the cases it remains unknown.
Pathways of protein degradation: - Huntington’s disease and Parkinson’s diseases have connections with the intracellular toxic proteins’ accumulation; however its onset occurs late. The causes of these diseases are due to the accumulation of proteinopathies types of proteins. The very protein aggregation takes place in the following structures.
nucleus, read with the type of. Spinocerebellar ataxia type 1 (SCA1)
cytosol, read with the type of. Parkinson's & Huntington's
extracellularly excreted proteins, read with the type of amyloid-β in Alzheimer’s disease
Endoplasmic reticulum (ER), (mostly found in the cases of neuroserpin mutations that leads to familial encephalopathy with the neuroserpin inclusion bodies)
Many of the neurodegenerative diseases come under the classification of proteopathies because they are related to misfolded proteins’ aggregation.