Fig. 3. Altered proteostasis and ribostasis are common pathogenic mechanisms in neurodegenerative diseases. Under physiological conditions, newly synthesized proteins fold correctly to ensure their normal functions, and misfolded proteins are targeted to maintain proteostasis in degradation systems. Two protein degradation systems, the UPS and autophagy, are essential to maintaining cellular homeostasis. However, mutations and/or PTMs of disease-associated proteins (Aβ and tau in Alzheimer’s disease, α-syn in Parkinson’s disease, and SOD1, TDP-43, and FUS in ALS) form pathogenic aggregates and induce degradation system dysregulation. During stress conditions, ALS-associated RBPs (TDP-43 and FUS) are often reversibly assembled into SGs with target RNAs, and prolonged SGs are removed through the autophagy system. Chronic stress and/or RBP mutations lead to the irreversible accumulation of SGs and inhibit the normal functions of RBPs and target RNAs in maintaining RNA metabolism. Aβ, amyloid-beta; ALS, amyotrophic lateral sclerosis; HSP, heat-shock protein; PTMs, posttranslational modifications; SGs, stress granules; SOD1, superoxide dismutase-1; UPS, ubiquitin proteasome system; α-syn, α-synuclein.