Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, AMYOTROPHIC-LATERAL-SCLEROSIS, UBIQUITIN-PROTEASOME SYSTEM, MOTOR-NEURON DISEASE, ALPHA-SYNUCLEIN TOXICITY, FRONTOTEMPORAL DEMENTIA, ALZHEIMERS-DISEASE, DNA-DAMAGE, PARKINSON-DISEASE, OXIDATIVE STRESS, AMYLOID-BETA, DNA and RNA defects, cytoskeletal defects, energy homeostasis, hallmarks, inflammation, neurodegeneration, neurodegenerative disease, protein aggregation, proteostasis, synaptic and neuronal network dysfunction, Humans, Neurodegenerative Diseases, Proteostasis, Protein Aggregation, Pathological, Cell Death, Cytoskeleton, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

Abstract:

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks of NDD: pathological protein aggregation, synaptic and neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. We describe the hallmarks, their biomarkers, and their interactions as a framework to study NDDs using a holistic approach. The framework can serve as a basis for defining pathogenic mechanisms, categorizing different NDDs based on their primary hallmarks, stratifying patients within a specific NDD, and designing multi-targeted, personalized therapies to effectively halt NDDs.