New Insights into the Molecular Bases of Familial Alzheimer’s Disease
Like several neurodegenerative disorders, such as Prion and Parkinson diseases, Alzheimer’s disease (AD) is characterized by spreading mechanism of aggregated proteins in the brain in a typical “prion-like” manner. Recent genetic studies have identified in four genes associated with inherited AD (am...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/10/2/26 |
| _version_ | 1797570151833403392 |
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| author | Valeria D’Argenio Daniela Sarnataro |
| author_facet | Valeria D’Argenio Daniela Sarnataro |
| author_sort | Valeria D’Argenio |
| collection | DOAJ |
| description | Like several neurodegenerative disorders, such as Prion and Parkinson diseases, Alzheimer’s disease (AD) is characterized by spreading mechanism of aggregated proteins in the brain in a typical “prion-like” manner. Recent genetic studies have identified in four genes associated with inherited AD (amyloid precursor protein-<i>APP</i>, Presenilin-1, Presenilin-2 and Apolipoprotein E), rare mutations which cause dysregulation of APP processing and alterations of folding of the derived amyloid beta peptide (Aβ). Accumulation and aggregation of Aβ in the brain can trigger a series of intracellular events, including hyperphosphorylation of tau protein, leading to the pathological features of AD. However, mutations in these four genes account for a small of the total genetic risk for familial AD (FAD). Genome-wide association studies have recently led to the identification of additional AD candidate genes. Here, we review an update of well-established, highly penetrant FAD-causing genes with correlation to the protein misfolding pathway, and novel emerging candidate FAD genes, as well as inherited risk factors. Knowledge of these genes and of their correlated biochemical cascade will provide several potential targets for treatment of AD and aging-related disorders. |
| first_indexed | 2024-03-10T20:21:51Z |
| format | Article |
| id | doaj.art-05185b1cfa174640bbbd9ca1b0d965f6 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T20:21:51Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-05185b1cfa174640bbbd9ca1b0d965f62023-11-19T22:06:43ZengMDPI AGJournal of Personalized Medicine2075-44262020-04-011022610.3390/jpm10020026New Insights into the Molecular Bases of Familial Alzheimer’s DiseaseValeria D’Argenio0Daniela Sarnataro1CEINGE-Biotecnologie Avanzate scarl, via G. Salvatore 486, 80145 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, Federico II University, via S. Pansini 5, 80131 Naples, ItalyLike several neurodegenerative disorders, such as Prion and Parkinson diseases, Alzheimer’s disease (AD) is characterized by spreading mechanism of aggregated proteins in the brain in a typical “prion-like” manner. Recent genetic studies have identified in four genes associated with inherited AD (amyloid precursor protein-<i>APP</i>, Presenilin-1, Presenilin-2 and Apolipoprotein E), rare mutations which cause dysregulation of APP processing and alterations of folding of the derived amyloid beta peptide (Aβ). Accumulation and aggregation of Aβ in the brain can trigger a series of intracellular events, including hyperphosphorylation of tau protein, leading to the pathological features of AD. However, mutations in these four genes account for a small of the total genetic risk for familial AD (FAD). Genome-wide association studies have recently led to the identification of additional AD candidate genes. Here, we review an update of well-established, highly penetrant FAD-causing genes with correlation to the protein misfolding pathway, and novel emerging candidate FAD genes, as well as inherited risk factors. Knowledge of these genes and of their correlated biochemical cascade will provide several potential targets for treatment of AD and aging-related disorders.https://www.mdpi.com/2075-4426/10/2/26Alzheimer’s disease<i>APP</i> mutations<i>APOE</i> alleles<i>PSEN1</i><i>PSEN2</i>germline mutations |
| spellingShingle | Valeria D’Argenio Daniela Sarnataro New Insights into the Molecular Bases of Familial Alzheimer’s Disease Journal of Personalized Medicine Alzheimer’s disease <i>APP</i> mutations <i>APOE</i> alleles <i>PSEN1</i> <i>PSEN2</i> germline mutations |
| title | New Insights into the Molecular Bases of Familial Alzheimer’s Disease |
| title_full | New Insights into the Molecular Bases of Familial Alzheimer’s Disease |
| title_fullStr | New Insights into the Molecular Bases of Familial Alzheimer’s Disease |
| title_full_unstemmed | New Insights into the Molecular Bases of Familial Alzheimer’s Disease |
| title_short | New Insights into the Molecular Bases of Familial Alzheimer’s Disease |
| title_sort | new insights into the molecular bases of familial alzheimer s disease |
| topic | Alzheimer’s disease <i>APP</i> mutations <i>APOE</i> alleles <i>PSEN1</i> <i>PSEN2</i> germline mutations |
| url | https://www.mdpi.com/2075-4426/10/2/26 |
| work_keys_str_mv | AT valeriadargenio newinsightsintothemolecularbasesoffamilialalzheimersdisease AT danielasarnataro newinsightsintothemolecularbasesoffamilialalzheimersdisease |