Neurodegenerative Pathologies and Stress Response Signaling

Oxidative stress is considered to be involved AD because it causes multiple damages to neuronal cells. It is reported that lipid peroxidation and its neurotoxic by-products 4-hydroxynonenal (HNE) and acrolein were increased in an AD brain (Williams et al. 2006). Mitochondrial membrane lipids are vulnerable to oxidative stress, thus oxidative stress 

FIGURE 10.7. Transforming growth factor p (TGF-p) signaling in parallel with insulln/lnsulin growth factor (IGF) signaling. 

The mechanism of action of causation and the progression of PD remain unclear, but oxidative stress, inflammation, dysfunction of microglia, and the increase of misfolding of alpha-synuclein are considered to be major factors (Whitton 2007). 

In normal state, L-DOPA is biosynthesized from L-tyrosine, then it is converted by the enzyme tyrosine hydroxylase (TH) to form dopamine in the dopaminergic neurons (Nakashima et al. 2011). When dopamine is released from substantia nigra pars compacta (SNpc), it binds to the D1 type receptor and D2 type receptor resulting in an increase or decrease of PKA. 

PD is caused by the depletion of dopamine in the striatum via the development of degenerated dopamine neurons in the SNpc (Hara etal. 

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