From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer’s and Parkinson’s diseases

Abstract

Two of the most common neurodegenerative disorders – Alzheimer’s and Parkinson’s diseases – are characterized by synaptic dysfunction and degeneration that culminate in neuronal loss due to abnormal protein accumulation. The intracellular aggregation of hyper-phosphorylated tau and the extracellular aggregation of amyloid beta plaques form the basis of Alzheimer’s disease pathology. The major hallmark of Parkinson’s disease is the loss of dopaminergic neurons in the substantia nigra pars compacta, following the formation of Lewy bodies, which consists primarily of alpha-synuclein aggregates. However, the discrete mechanisms that contribute to neurodegeneration in these disorders are still poorly understood. Both neuronal loss and impaired adult neurogenesis have been reported in animal models of these disorders. Yet these findings remain subject to frequent debate due to a lack of conclusive evidence in post mortem brain tissue from human patients. While some publications provide significant findings related to axonal regeneration in Alzheimer’s and Parkinson’s diseases, they also highlight the limitations and obstacles to the development of neuroregenerative therapies. In this review, we summarize in vitro and in vivo findings related to neurogenesis, neuroregeneration and neurodegeneration in the context of Alzheimer’s and Parkinson’s diseases.

Keywords

• alpha-synuclein; amyloid beta plaques; autophagy; dopaminergic neurons; human ipscs; mitochondrial dysfunction; scrna sequencing; synaptic dysfunction; tau; wallerian degeneration