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Moderate stage , where there is notable cartilage loss in weight bearing regions, along with meniscal degeneration, evidence of osteophytes and subchondral sclerosis, and weakening of the quadriceps muscles

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However, in NDDs, chronic or overwhelming ER stress shifts the UPR toward maladaptive responses, contributing to neuronal dysfunction and death, e.g., Prolonged PERK activation has been implicated in AD, PD, and ALS, where it contributes to chronic ER stress and neuronal death